ЛИГАНДЫ TLR3, КОТОРЫЕ АКТИВИРУЮТ КАК ЭПИТЕЛИАЛЬНЫЕ, ТАК И МИЕЛОИДНЫЕ КЛЕТКИ

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УЛУЧШЕННАЯ ОЛИГОНУКЛЕОТИДНАЯ КОНСТРУКЦИЯ ТИПА НАНОЧАСТИЦЫ, ОБЛАДАЮЩАЯ ВЫСОКОЙ ЭФФЕКТИВНОСТЬЮ, И СПОСОБ ЕЕ ПОЛУЧЕНИЯ

Изобретение относится к области биотехнологии, конкретно к самособирающейся в наночастицу олигонуклеотидной конструкции, и может быть использовано в медицине. Олигонуклеотидная конструкция согласно настоящему изобретению может быть полезной в качестве системы доставки на основе олигонуклеотида нового типа, а также инструмента для лечения злокачественных заболеваний, инфекционных заболеваний и т.п. Полимерное соединение, входящее в состав конструкции, связано с антисмысловым олигонуклеотидом посредством ковалентной связи для улучшения стабильности in vivo олигонуклеотида и эффективности его доставки в целевую клетку. В сравнении с известными аналогами заявленная олигонуклеотидная конструкция оптимизирована в отношении гомогенного материала, упрощена схема ее твердофазного синтеза, а размер двухцепочечной конструкции олиго-РНК может быть точно отрегулирован посредством контроля числа повторов блока и гидрофильного материала. 8 н. и 21 з.п. ф-лы, 18 ил., 4 табл., 6 пр.

ТЕРАПЕВТИЧЕСКОЕ СРЕДСТВО ПРОТИВ ЗАБОЛЕВАНИЙ, СВЯЗАННЫХ С ГИБЕЛЬЮ КЛЕТОК ЭНДОТЕЛИЯ РОГОВИЦЫ, ОБУСЛОВЛЕННОЙ СОСТОЯНИЕМ ЭНДОПЛАЗМАТИЧЕСКОГО РЕТИКУЛУМА

Группа изобретений относится к медицине, а именно к офтальмологии, и может быть использована для лечения или профилактики заболевания, расстройств или состояний, вызванных стрессом эндоплазматического ретикулума в эндотелии роговой оболочки глаза. Для этого используют терапевтическое или профилактическое средство в виде глазных капель, содержащее ингибитор сигнального пути NGF-beta. Предпочтительно ингибитор сигнального пути содержит 4-[4-(1,3-бензодиоксол-5-ил)-5-(2-пиридинил)-1H-имидазол-2-ил]бензамид, а также дополнительный фармацевтический ингредиент, выбранный из ингибиторов киназы Rho или стероидов. Группа изобретений обеспечивает способ получения терапевтического профилактического средства против заболеваний, расстройств или состояний, вызванных стрессом эндоплазматического ретикулума в эндотелии роговой оболочки глаза. 3 н. и 12 з.п. ф-лы, 14 ил., 15 пр.

Способ изменения функционального состояния мРНК, обеспечивающий ее избирательное и специфическое распознавание

Предложенная группа изобретений относится к области медицины. Предложена конструкция для связывания последовательностей-мишеней нуклеиновой кислоты, содержащая две комплементарные последовательности олигонуклеотидов длиной до 20 нуклеотидов, отдаленных друг от друга посредством полимерного связующего фрагмента, конечная длина которого составляет от 10 до 100 ангстрем на основе расстояния между нуклеотидами в линейной, полностью удлиненной нуклеиновой кислоте. Предложен раствор для нацеливания на опухолевые клетки, содержащий указанную конструкцию. Предложен способ связывания конструкции с последовательностью-мишенью нуклеиновой кислоты, обеспечивающий избирательное распознавание нуклеиновой кислоты-мишени, включающий контактирование нуклеиновой кислоты-мишени с конструкцией для формирования гетеродуплекса. Предложен способ лечения пациента, страдающего от рака и способ диагностики рака. Предложенная группа изобретений обеспечивает образование стабильного гетеродуплекса и избирательное распознавание ...

ПОЛИНУКЛЕОТИД С УКОРОЧЕННОЙ ЦЕПЬЮ И СПОСОБ ЕГО ПОЛУЧЕНИЯ

В настоящем изобретении предлагается полинуклеотид со средней длиной цепи от 0,1 до 1 тыс. оснований, в котором доля 2’-5’ фосфодиэфирных связей составляет от 0,1 до 3% от общего числа фосфодиэфирных связей, или его соль. Полинуклеотид представляет собой полиинозиновую кислоту (поли(I)), полицитидиловую кислоту (поли(С)), полиадениловую кислоту (поли(А)) или полиуридиловую кислоту (поли(U)). Способ получения полинуклеотида включает гидролиз в растворе при pH от 7 до 10 и температуре от 20 до 110°С или обработку фосфодиэстеразой при pH от 4 до 9 и температуре от 20 до 60°С. Также изобретение относится к фармацевтической композиции, представляющей собой интерферон-индуцирующий агент, иммуноактивирующий агент и др., включающей указанный полинуклеотид. 5 с. и 3 з.п. ф-лы, 8 табл.

КОНКАТЕМЕРЫ ДЛЯ ИММУНОМОДУЛЯЦИИ

Изобретение относится к области биохимии. Предложена конкатемерная молекула некодирующей нуклеиновой кислоты, содержащая по меньшей мере четыре одноцепочечных участка с неметилированными CG-мотивами, для модуляции активности иммунной системы человека и животного. Рассмотрены содержащие конкатемерную молекулу фармацевтические композиции и набор, а также применение для изготовления средства для модуляции иммунной системы или для модуляции активности иммунной системы человека или животного молекулы и композиции по изобретению. Данное изобретение может найти дальнейшее применение в качестве иммуномодулятора в терапии различных заболеваний. 5 н. и 15 з.п. ф-лы, 4 ил.

СРЕДСТВО ДЛЯ ЛЕЧЕНИЯ ФИБРОЗА ПОЧЕК

Настоящее изобретение относится к носителю для доставки вещества в продуцирующие внеклеточный матрикс клетки в почке, причем носитель содержит ретиноид в качестве нацеливающего агента. Настоящее изобретение также относится к средству для лечения фиброза почек вследствие диабетического нефрита и уменьшения фиброза в мезангиальной области и окружающей среде тубулярных клеток, в котором применяется указанный носитель. Кроме того, настоящее изобретение относится к способам получения носителя и средства, наборам для получения и способу и тому подобному для лечения фиброза почек с применением средства для лечения фиброза почек. 4 н. и 6 з.п. ф-лы, 3 ил., 3 пр.

АНТИТЕЛА ПРОТИВ СИГЛЕКА-15 ДЛЯ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЯ, СВЯЗАННОГО С ПОТЕРЕЙ КОСТНОЙ МАССЫ

Изобретение относится к области биотехнологии и иммунологии. Описаны новые антитела или антиген-связывающие фрагменты, которые специфично связываются с сиглеком-15. В некоторых вариантах воплощения антиген-связывающие фрагменты могут блокировать биологическую активность сиглека-15 и полезны в составе композиции для лечения потери костной массы, в частности заболеваний костей, при которых повышена экспрессия сиглека-15 на клеточной поверхности, таких как состояния, при которых повышена активность остеокластов по деградации кости. Изобретение также относится к клеткам, экспрессирующим антитела или антиген-связывающие фрагменты, такие как моноклональные, гуманизированные или химерные антитела. Дополнительно также раскрыты способы детекции и лечения потери костной массы, заболеваний, связанных с потерей костной массы или онкологического заболевания с применением антител или антиген-связывающих фрагментов. 15 н. и 11 з.п. ф-лы, 20 ил., 6 табл., 4 пр.

СПОСОБ, КОМПОЗИЦИЯ И НАБОР ДЛЯ СТАБИЛИЗАЦИИ ДЕЗОКСИРИБОНУКЛЕИНОВЫХ КИСЛОТ В БИОЛОГИЧЕСКИХ ОБРАЗЦАХ

Группа изобретений относится к биотехнологии, в частности к области стабилизации дезоксирибонуклеиновой кислоты (ДНК) человека и микроорганизмов, присутствующей в сложных биологических образцах, таких как фекалии. Предложены способ, водная композиция и набор для стабилизации ДНК, содержащейся в фекалиях или образце, загрязненном фекалиями, при температуре окружающей среды. Указанный биологический образец приводят в контакт с водной композицией, содержащей хелатирующее средство, выбранное из этилендиаминтетрауксусной кислоты (EDTA) или 1,2-циклогександиаминтетрауксусной кислоты (CDTA), в концентрации от приблизительно 150 мМ до приблизительно 600 мМ и имеющей рН от 9,5 до 11,5. Полученную смесь гомогенизируют и хранят при температуре окружающей среды. Группа изобретений обеспечивает быстрый и эффективный захват и стабилизацию ДНК и «мгновенную фиксацию» профилей суммарной ДНК в биологических образцах при температуре окружающей среды в течение длительных периодов времени. 3 н. и 47 з.п. ф-лы ...

КОМПОЗИЦИИ И СПОСОБЫ МОДУЛИРОВАНИЯ ЭКСПРЕССИИ HBV И TTR

Изобретение относится к применимому в медицине соединению, содержащему модифицированный олигонуклеотид и конъюгирующую группу, при этом модифицированный олигонуклеотид состоит из 12-30 связанных нуклеозидов и содержит последовательность азотистых оснований, включающую часть из по меньшей мере 8 смежных азотистых оснований, комплементарную равной по длине части SEQ ID NO: 1, при этом последовательность азотистых оснований модифицированного олигонуклеотида по меньшей мере на 90% комплементарна SEQ ID NO: 1, где конъюгирующая группа содержитгде конъюгирующая группа связана с модифицированным олигонуклеотидом на 5'-конце или 3'-конце модифицированного олигонуклеотида. Предложено новое соединение и композиция на его основе, эффективные для производства лекарственного средства для лечения заболевания, опосредованного НВV. 4 н. и 36 з.п. ф-лы, 113 пр., 108 табл.

СОПРЯЖЕННЫЕ АНТИСМЫСЛОВЫЕ СОЕДИНЕНИЯ И ИХ ПРИМЕНЕНИЕ

Изобретение относится к области биотехнологии и медицине. Предложено соединение, сопряженное с тремя N-ацетилгалактозаминовыми лигандами. Соединение имеет структуру XXVI:где Тпредставляет собой группу, содержащую нуклеозид, нуклеотид, мономерную субъединицу, реакционноспособный сложный эфир, линкер, расщепляемый фрагмент или олигомерное соединение. Соединение обладает улучшенной активностью в клетках печени in vivo и пригодно для применения в способе лечения метаболического расстройства или в способе лечения сердечно-сосудистого расстройства. 15 з.п. ф-лы, 120 табл., 112 пр.

ЛЕЧЕНИЕ ЗАБОЛЕВАНИЙ, СВЯЗАННЫХ С NANOG, ПУТЕМ ИНГИБИРОВАНИЯ ПРИРОДНОГО АНТИСМЫСЛОВОГО ТРАНСКРИПТА NANOG

Изобретение относится к биохимии. Описаны способы повышения экспрессии полинуклеотида NANOG с помощью олигонуклеотидов длиной от 19 до 30 нуклеотидов. Описаны соответствующие олигонуклеотиды и композиция, содержащая их. Также описан способ предотвращения или лечения заболевания, ассоциированного с по меньшей мере одним полинуклеотидом NANOG и/или по меньшей мере одним продуктом, кодируемым указанным полинуклеотидом, включающий: введение пациенту терапевтически эффективной дозы по меньшей мере одного описанного олигонуклеотида. 9 н. и 26 з.п. ф-лы, 1 ил., 1 табл., 2 пр.

МОДУЛЯЦИЯ ЭКСПРЕССИИ ФАКТОРА 11

Изобретение относится к области биотехнологии. Описаны антисмысловые соединения, способы снижения уровня фактора 11 и способы лечения или предупреждения тромбоэмболических осложнений у индивидуума, нуждающегося в этом. Примерами патологических состояний, которые могут быть подвергнуты лечению путем введения антисмысловых соединений, нацеленных на фактор 11, являются тромбоз, эмболия и тромбоэмболия, такие как тромбоз глубокой вены, эмболия легких, инфаркт миокарда и инсульт. Антисмысловые соединения, нацеленные на фактор 11, могут быть также использованы в качестве профилактических средств для устранения риска развития у индивидуумов тромбоза и эмболии. 5 н. и 52 з.п. ф-лы, 169 табл., 47 пр.

ОПОСРЕДУЕМОЕ РНК-ИНТЕРФЕРЕНЦИЕЙ ИНГИБИРОВАНИЕ ЭКСПРЕССИИ ГЕНОВ ВИРУСА ГЕПАТИТА B (HBV) С ПРИМЕНЕНИЕМ МАЛОЙ ИНТЕРФЕРИРУЮЩЕЙ НУКЛЕИНОВОЙ КИСЛОТЫ (миНК)

Изобретение относится к биотехнологии. Описаны соединения, композиции и способы исследования, диагностики и лечения симптомов, заболеваний и состояний, реагирующих на модуляцию экспрессии и/или активности генов HBV и/или модуляцию экспрессии пути генов HBV. Описаны двухцепочечные молекулы нуклеиновой кислоты, такие как молекулы малой интерферирующей нуклеиновой кислоты (миНК), малой интерферирующей РНК (миРНК), двухцепочечной РНК (дцРНК), микро-РНК (мкРНК) и короткошпилечной РНК (кшРНК), опосредующие РНК-интерференцию (РНКи) против экспрессии генов HBV. Изобретение расширяет арсенал средств для генной терапии. 11 н. и 6 з.п. ф-лы, 11 табл., 6 пр., 10 ил.

МОЛЕКУЛЫ НОВЫХ ИСКУССТВЕННЫХ НУКЛЕИНОВЫХ КИСЛОТ

Изобретение относится к молекуле искусственной нуклеиновой кислоты, для экспрессии белка или пептида in vitro, включающей по меньшей мере одну открытую рамку считывания и по меньшей мере один элемент 3'-нетранслируемой области, причем по меньшей мере один элемент 3'-UTR продлевает и/или увеличивает выработку белка указанной молекулы искусственной нуклеиновой кислоты и происходит от стабильной мРНК, в которой по меньшей мере один элемент 3'-UTR содержит или состоит из последовательности нуклеиновой кислоты, которая происходит от 3'-UTR транскрипта – GNAS. Изобретение также относится к вектору и клетке для обеспечения транскрипции молекулы нуклеиновой кислоты, способу получения белка или пептида, синтезируемого искусственной молекулой нуклеиновой кислоты и применению элемента 3'-UTR и/или элемента 5'-UTR для получения белка или пептида in vitro за счет увеличения и/или продления его выработки молекулой искусственной нуклеиновой кислоты или вектором. 5 н. и 14 з.п. ф-лы, 9 пр., 30 ил., 10 ...

ЛЕЧЕНИЕ ЗАБОЛЕВАНИЙ, СВЯЗАННЫХ С КОЛОНИЕСТИМУЛИРУЮЩИМ ФАКТОРОМ 3 (CSF3), ПУТЕМ ИНГИБИРОВАНИЯ ПРИРОДНОГО АНТИСМЫСЛОВОГО ТРАНСКРИПТА K CSF3

Изобретение относится к биохимии. Описаны модифицированные олигонуклеотиды длиной от 15 до 30 нуклеотидов, содержащие по меньшей мере одну модификацию, причем указанная по меньшей мере одна модификация выбрана из: по меньшей мере одного модифицированного фрагмента сахара; по меньшей мере одной модифицированной межнуклеотидной связи; по меньшей мере одного модифицированного нуклеотида; и их комбинаций. Причем указанные олигонуклеотиды специфически гибридизуются с природным антисмысловым полинуклеотидом гена CSF3 и имеют последовательность, по меньшей мере на 80% идентичную последовательности, обратно комплементарной участку в рамках нуклеотидов с 1 по 742 SEQ ID NO: 2, или имеют последовательность, по меньшей мере на 80% идентичную участку последовательности SEQ ID NO: 1. Изобретение также относится к применению таких антисмысловых олигонуклеотидов для лечения заболеваний и расстройств, связанных с экспрессией CSF3. Изобретение расширяет арсенал средств для лечения заболеваний и расстройств ...

КОМПОЗИЦИИ И СПОСОБЫ МОДУЛЯЦИИ SMN2 СПЛАЙСИНГА У СУБЪЕКТА

Изобретение относится к области медицины и предназначено для лечения спинальной мышечной атрофии (СМА). Способ включает введение посредством болюсной инъекции в интратекальное пространство субъекта, являющегося человеком, антисмыслового соединения, содержащего антисмысловой олигонуклеотид, состоящий из 18 связанных нуклеозидов, где каждая межнуклеозидная связь олигонуклеотида представляет собой фосфоротиоатную связь, где каждый нуклеозид олигонуклеотида представляет собой 2'-МОЭ нуклеозид и где введение антисмыслового соединения усиливает включение экзона 7 в SMN2 мРНК транскриптах у субъекта, являющегося человеком. Изобретение обеспечивает эффективное лечение СМА типов I, II и III. 11 з.п. ф-лы, 13 ил., 14 табл., 14 пр.

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Настоящая группа изобретений относится к медицине, а именно к онкологии, и касается лечения рака. Для этого субъекту со снижением или отсутствием N-миристоилтрансферазы 2 (NMT2) вводят эффективное количество ингибитора NMT. Это обеспечивает эффективное лечение данной формы рака. 5 н. и 56 з.п. ф-лы, 6 ил., 7 пр., 1 табл.

ИНЪЕКЦИОННАЯ КОМПОЗИЦИЯ ПОЛИДЕЗОКСИРИБОНУКЛЕОТИДОВ ДЛЯ ЛЕЧЕНИЯ КОСТНО-СУСТАВНЫХ ЗАБОЛЕВАНИЙ

Описана фармацевтическая композиция на основе полидезоксирибонуклеотидов, экстрагированных из естественных источников. Композиция содержит фракцию полидезоксирибонуклеотидов, экстрагированных из спермы рыб, где указанные полидезоксирибонуклеотиды обладают полимерными цепями с различными молекулярными массами от 70 килодальтонов до 240 килодальтонов. Композиция пригодна для применения в качестве терапевтического средства при лечении костно-суставных патологий, особенно остеоартрита, путем внутрисуставной инъекции, обеспечивая необходимую вязкость синовиальной жидкости. 2 н. и 6 з.п. ф-лы, 13 ил.

ЛЕЧЕНИЕ ЗАБОЛЕВАНИЙ, СВЯЗАННЫХ С СУБСТРАТОМ РЕЦЕПТОРА ИНСУЛИНА 2 (IRS2), ПУТЕМ ИНГИБИРОВАНИЯ ПРИРОДНОГО АНТИСМЫСЛОВОГО ТРАНСКРИПТА К IRS2

Изобретение относится к олигонуклеотиду длиной от 15 до 30 нуклеотидов, который специфически гибридизуется с природной антисмысловой последовательностью IRS2 и имеет последовательность, по меньшей мере на 80% идентичную последовательности, обратно комплементарной участку последовательности SEQ ID NO: 3, или имеет последовательность, по меньшей мере на 80% идентичную участку последовательности SEQ ID NO: 1, причем указанный олигонуклеотид необязательно содержит одну или более модификаций, выбранных из следующих: по меньшей мере один модифицированный фрагмент сахара, по меньшей мере одна модифицированная межнуклеозидная связь, по меньшей мере один модифицированный нуклеотид и их комбинации. Изобретение также относится к их применению для лечения заболеваний и расстройств, связанных с экспрессией IRS2. 5 н. и 23 з.п. ф-лы, 4 ил., 2 пр.

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Изобретение относится к пригодному для применения в медицине соединению, содержащему модифицированный олигонуклеотид и конъюгирующую группупри этом модифицированный олигонуклеотид состоит из 20 связанных азотистых оснований, комплементарных равной по длине части азотистых оснований 3533-3552 в SEQ ID NO: 3, при этом модифицированный олигонуклеотид содержит сегмент гэп, состоящий из связанных дезоксинуклеозидов; сегмент крыла 5', состоящий из связанных нуклеозидов; сегмент крыла 3', состоящий из связанных нуклеозидов; при этом сегмент гэп расположен между сегментом крыла 5' и сегментом крыла 3', и при этом каждый нуклеозид каждого сегмента крыла содержит модифицированный сахар, и где по меньшей мере один нуклеозид содержит модифицированное азотистое основание; и модифицированный олигонуклеотид содержит по меньшей мере одну модифицированную межнуклеозидную связь. Предложены новые конъюгаты модифицированных олигонуклеотидов и композиции на их основе для лечения, предупреждения или замедления ...

ДВУХЦЕПОЧЕЧНАЯ МОЛЕКУЛА РНК ДЛЯ ОБЕСПЕЧЕНИЯ КЛЕТКИ АКТИВНОСТЬЮ miR-34a

Изобретение относится к области молекулярной биологии и медицины. Предложена двухцепочечная молекула РНК с тупыми концами длиной 23 пары оснований для обеспечения клетки активностью miR-34a. При этом молекула РНК содержит активную цепь, имеющую SEQ ID NO: 2 от 5' к 3', и полностью комплементарную цепь-«пассажир», имеющую нуклеотидную последовательность, состоящую из SEQ ID NO: 4. Цепь-«пассажир» содержит 2'-OMe модификации сахара в нуклеотидах в положениях 1, 2, 22 и 23, а также терминальную модификацию нуклеотида на 5'-конце. Двухцепочечные молекулы РНК по изобретению являются устойчивыми к нуклеазному расщеплению, активными и специфически гибридизующимися с правильной мРНК-мишенью. 14 з.п. ф-лы, 19 табл., 11 пр.

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Изобретение относится к области биофармацевтических и терапевтических средств. Предложены ионизируемые соединения, а также фармацевтическая композиция на основе ионизируемых соединений. Технический результат – получение ионизируемых соединений, которые используются для доставки и распределения действующих агентов или лекарственных средств. 12 н. и 16 з.п. ф-лы, 32 ил., 10 табл., 40 пр.

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Настоящее раскрытие относится к медицине, в частности к способу получения РНК-липоплексных частиц для доставки РНК в ткани-мишени после парентерального введения и композиции, содержащей такие частицы. Для осуществления указанного способа смешивают раствор, содержащий РНК и имеющий ионную силу, соответствующую хлориду натрия в концентрации от около 50 мМ до около 300 мМ, и раствор, содержащий катионные липосомы в контролируемых условиях смешивания. При этом объединенный поток первого раствора и второго раствора характеризуется числом Рейнольдса более 300. В результате получают РНК-липоплексные частицы, имеющие средний диаметр, который находится в диапазоне от около 300 нм до около 500 нм, и имеющие индекс полидисперсности менее чем 0,2. Настоящее изобретение позволяет повысить эффективность трансляции РНК в пептид или белок, который она кодирует при доставке РНК в клетку-мишень, а также повысить стабильность композиций при хранении без существенной потери качества продукта, в частности, ...

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Изобретение относится к области биохимии, в частности к композиции против клещей, содержащей в эффективном количестве молекулу нуклеиновой кислоты, имеющую последовательность, которая по меньшей мере на 96% комплементарна или идентична по меньшей мере 21 смежному нуклеотиду последовательности гена кальмодулина, а также к ее использованию для снижения паразитизмана медоносной пчеле и для селективной обработки видов членистоногих от. Также раскрыт конструкт для ингибирования гена Varroa destructor, содержащий нуклеиновую кислоту, которая кодирует дцРНК, содержащую последовательность нуклеиновой кислоты, которая по меньшей мере на 96% идентична или комплементарна по меньшей мере 21 смежному нуклеотиду последовательности гена кальмодулина. Изобретение позволяет эффективно снижать паразитизмна медоносной пчеле. 6 н. и 36 з.п. ф-лы, 7 ил., 6 табл., 11 пр.

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Изобретение относится к области биотехнологии. Описана группа изобретений, включающая конструкцию для ДНК-направленной РНК-интерференции (ddRNAi), вектор экспрессии, содержащий вышеуказанную конструкцию, композицию для ингибирования экспрессии белка PABPN1, который является причиной окулофарингеальной мышечной дистрофии (OPMD), способ подавления экспрессии белка PABPN1, способ лечения окулофарингеальной мышечной дистрофии (варианты) и набор для лечения окулофарингеальной мышечной дистрофии. В одном из вариантов реализации изобретения конструкция ddRNAi содержит в себе последовательность ДНК, кодирующую шпилечную РНК, содержащую эффекторную последовательность из по меньшей мере 17 смежных нуклеотидов, которая по существу комплементарна области транскрипта РНК, соответствующей белку PABPN1, где область транскрипта РНК приведена под любым из SEQ ID NO: 1-3. Изобретение расширяет арсенал средств для ДНК-направленной РНК-интерференции. 7 н. и 26 з.п. ф-лы, 8 ил., 5 табл., 4 пр.

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Изобретение относится к композиции для лечения или предупреждения ожирения. Предложено применение фармацевтической композиции, содержащей амфирегулин-специфический двухцепочечный олигонуклеотид, двухцепочечную олиго-РНК, которая содержит гидрофильные и гидрофобные соединения, соединенные с амфирегулин-специфическим двухцепочечным олигонуклеотидом, или наночастицы, содержащие двухцепочечную олиго-РНК. Амфирегулин-специфический двухцепочечный олигонуклеотид содержит последовательность, выбранную из SEQ ID NO: 10, 11 и 12, и антисмысловую цепь, комплементарную последовательности смысловой цепи. Изобретение обеспечивает потерю веса, снижение коэффициента пищевой эффективности, уменьшение подкожного жира, уменьшение висцерального жира, уменьшение площади адипоцитов и ингибирование адипогенеза печени. 23 з.п. ф-лы, 28 ил., 10 табл., 10 пр.

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Группа изобретений касается лечения заболеваний, связанных с тубулин карбоксипептидазой (TCP), и скрининга соединений, пригодных для лечения таких заболеваний. Предлагается применение ингибитора экспрессии или активности комплекса вазогибин/SVBP (малый вазогибин-связывающий белок) для лечения заболевания, связанного с циклом детирозинирования/тирозинирования тубулина тубулин карбоксипептидазой, у субъекта, который в этом нуждается. Предлагается также применение фармацевтической композиции, содержащей ингибитор экспрессии или активности комплекса вазогибин/SVBP для лечения указанного выше заболевания. Заболевание, связанное с TCP, представляет собой неврологическое нарушение (в частности, рассеянный склероз, инсульт, боковой амиотрофический склероз, болезнь Паркинсона, болезнь Хантингтона и болезнь Альцгеймера) или сердечно-сосудистое заболевание (в частности, инфаркт миокарда, инфаркт миокарда, индуцирующий сердечно-сосудистую дисфункцию, сердечную недостаточность, кардиомиопатию и дистрофинопатию ...

КОМПОЗИЦИЯ ДЛЯ ЛЕЧЕНИЯ СОСТОЯНИЙ, ЧУВСТВИТЕЛЬНЫХ ИЛИ ВОСПРИИМЧИВЫХ К ВОЗДЕЙСТВИЮ ЛОЖНОСПАРЕННОЙ DS РНК

Изобретение относится к медицине. Цель - повышение стабильности. Композиция содержит носитель, ложноспаренную dsРНК, поверхностно-активное вещество в определенных количествах. Ложноспаренная dsРНК содержит участки разрыва связи и имеет формулу rIn•r (C11-14• V)n, где n - целое число от 4 до 29. 2 табл.

СПОСОБ ЛЕЧЕНИЯ ПОСТРАДАВШИХ С ТЯЖЕЛОЙ СОЧЕТАННОЙ ТРАВМОЙ

Способ относится к медицине, а именно к травматологии, и может быть использовано для уменьшения количества осложнений у пострадавших с тяжелой сочетанной травмой. Для этого пациенту с тяжелой сочетанной травмой в послеоперационном периоде дополнительно к лечению вводят ежесуточно внутримышечно 75 мг дерината в течение 10 суток, начиная со следующих суток после травмы. 1 табл., 1 пр.

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Изобретение относится к медицине, в частности к оториноларингологии и может быть использовано для лечения больных с гнойными риносинуситами с сопутствующим сахарным диабетом 2 типа. Способ включает дополнительное назначение больным риносинуситом с сахарным диабетом 2 типа терапии дезоксирибонуклеатом натрия (деринат) в дозе 6 мг внутримышечно по схеме: 5 инъекций через день, далее 5 инъекций в режиме 2 раза в неделю. Использование изобретения позволяет достичь уменьшения длительности лечения, более стойкой и длительной ремиссии, снижения уровня сахара крови и риска развития осложнений заболевания. 1 табл., 3 пр.

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Изобретение относится к олигонуклеотидам и их производным для подавления экспрессии изопренилпротеинтрансфераз, фармацевтическим композициям, содержащим такие соединения, и к использованию таких композиций олигонуклеотидов для лечения или терапии заболеваний человека или животных, вызванных ненормальной и/или нерегулируемой пролиферацией. Олигонуклеотиды имеют формулу (I): P - O-R (I), где Р либо отсутствует, либо представляет собой последовательность из одного или более оснований, выбранных из А (аденин), Т/(тимин), С (цитозин) или G (гуанин); О является последовательностью, выбранной из: SEQIDN1: AGAAGCCATG AT; SEQIDN2: GGACGTGACT GT; SEQIDN3: AAGGAGTAGC AG; SEQIDN4: CAGGCAGTAG CA; SEQIDN5: CCCGTCGTCC AT; SEQIDN6: CTGTCCCTGT AC; SEQIDN7: ACTTCTCTCT CC; SEQIDN8: ACTTGGTCCT AA; SEQIDN9: GCCATCATTC TG; SEQIDN10: GATCTGGACC AC; SEQIDN11: CTCAATAGCA TC; SEQIDN12: GTTTTTGGGG TG; SEQIDN13: TCTCACATCC TC; SEQIDN14: TTGTAAGAAC TG; SEQIDN15: GAAGTGCTTC TC; SEQIDN16: GCCTCTTTC AG; SEQIDN17: GGCATCTGTC ...

НУКЛЕИНОВЫЕ КИСЛОТЫ ДЛЯ ИНГИБИРОВАНИЯ ЭКСПРЕССИИ LPA В КЛЕТКЕ

Изобретение относится к области биотехнологии. Описана группа изобретений, включающая нуклеиновую кислоту для ингибирования экспрессии LPA в клетке, конъюгат для ингибирования экспрессии LPA в клетке (варианты), композицию для предотвращения, или лечения, или уменьшения риска развития сердечно-сосудистого заболевания и применение нуклеиновой кислоты, или конюгата, или композиции для предотвращения, или лечения, или уменьшения риска развития сердечно-сосудистого заболевания. В одном варианте реализации нуклеиновая кислота содержит по меньшей мере одну дуплексную область, которая содержит по меньшей мере часть первой цепи и по меньшей мере часть второй цепи, которая по меньшей мере частично комплементарна указанной первой цепи, причем указанная первая цепь по меньшей мере частично комплементарна по меньшей мере части РНК, транскрибированной с гена LPA. Изобретение расширяет арсенал средств для ингибирования экспрессии LPA в клетке. 5 н. и 21 з.п. ф-лы, 40 ил., 15 табл., 15 пр.

ПОЛУЧЕННЫЕ ИЗ БАКТЕРИЙ ИНТАКТНЫЕ МИНИ-КЛЕТКИ ДЛЯ ДОСТАВКИ ЛЕКАРСТВЕННЫХ СРЕДСТВ К ОПУХОЛЯМ МОЗГА

... 1. Способ лечения опухоли мозга у субъекта, включающий системное введение терапевтически эффективного количества композиции, состоящей из множества интактных, полученных из бактерий мини-клеток, отличающийся тем, что:(i) мини-клетки способны пассивно вытекать через отверстия в стенках кровеносных сосудов в опухоли мозга; и(ii) каждая мини-клетка указанного множества (а) содержит антитело, которое специфически распознает антиген опухолевых клеток и (b) заключает в себе антинеопластическое средство.2. Способ по п. 1, отличающийся тем, что указанное антинеопластическое средство представляет собой радиоактивный изотоп.3. Способ по п. 2, отличающийся тем, что радиоактивный изотоп выбран из иттрия-90, технеция-99m, йода-123, йода-131, рубидия-82, таллия-201, галлия-67, фтора-18, ксенона-133 или индия-111.4. Способ по п. 2, отличающийся тем, что радиоактивный изотоп присоединен к белку или углеводу на поверхности указанных мини-клеток.5. Способ по п. 4, отличающийся тем, что радиоактивный изотоп ...

КОМПОЗИЦИИ И СПОСОБЫ ДЛЯ МОДИФИКАЦИИ ЗАДАННОЙ ПОСЛЕДОВАТЕЛЬНОСТИ НУКЛЕИНОВОЙ КИСЛОТЫ-МИШЕНИ

... 1. Нуклеопротеиновая композиция для модификации заданного сайта-мишени в последовательности нуклеиновой кислоты-мишени в клетке-мишени, содержащая:(а) молекулу полинуклеотида, кодирующую химерный полипептид, при этом указанный полипептид содержит:(i) функциональный домен, способный к модифицированию указанного сайта-мишени, при этом функциональный домен лишен сайта специфического связывания нуклеиновой кислоты; и(ii) связующий домен, способный к взаимодействию с придающей специфичность нуклеиновой кислотой, при этом связующий домен лишен сайта специфического связывания нуклеиновой кислоты-мишени; и(b) придающую специфичность нуклеиновую кислоту (SCNA), содержащую:(i) нуклеотидную последовательность, комплементарную участку нуклеиновой кислоты-мишени, фланкирующему сайт-мишень; и(ii) участок распознавания, способный к специфическому присоединению к связующему домену полипептида;в соответствии с чем в результате сборки полипептида и SCNA внутри клетки-мишени образуется функциональный нуклеопротеиновый ...

СВЯЗЫВАЮЩИЕ SDF-1 НУКЛЕИНОВЫЕ КИСЛОТЫ И ИХ ПРИМЕНЕНИЕ

... 1. Молекула нуклеиновой кислоты, связывающаяся с SDF-1, где молекула нуклеиновой кислоты влияет на миграцию клеток. ! 2. Молекула нуклеиновой кислоты по п.1, где молекула нуклеиновой кислоты выбрана из группы, содержащей молекулы нуклеиновых кислот типа A, молекулы нуклеиновых кислот типа B, молекулы нуклеиновых кислот типа C и молекулы нуклеиновых кислот, имеющие последовательность нуклеиновой кислоты согласно любой из SEQ ID NO:142, SEQ ID NO:143 и SEQ ID NO:144. ! 3. Молекула нуклеиновой кислоты по п.2, где молекулы нуклеиновых кислот типа A содержат следующую коровую нуклеотидную последовательность: ! 5' AAAGYRACAHGUMAAXAUGAAAGGUARC 3' (SEQ ID NO:19), ! где XA либо отсутствует, либо представляет собой A. ! 4. Молекула нуклеиновой кислоты по п.2, где молекулы нуклеиновых кислот типа B содержат следующую коровую нуклеотидную последовательность: ! 5' GUGUGAUCUAGAUGUADWGGCUGWUCCUAGUYAGG 3' (SEQ ID NO:57). ! 5. Молекула нуклеиновой кислоты по п.2, где молекулы нуклеиновых кислот типа C содержат ...

ВЕЩЕСТВО И СПОСОБ МОДУЛЯЦИИ ПРОЛИФЕРАЦИИ И ДИФФЕРЕНЦИРОВКИ РЕГУЛЯТОРНЫХ, СТВОЛОВЫХ И ДРУГИХ СОМАТИЧЕСКИХ КЛЕТОК

... 1. Композиция, содержащая препарат тотальной РНК, выделенный из интактной лимфоидной клетки или ткани костного мозга здорового донора и/или из донорских лимфоидных клеток или ткани костного мозга здорового донора, подвергнутых активации Т-клеточной популяции.2. Композиция по п. 1, где указанная композиция или препарат тотальной РНК модулируют пролиферацию и/или дифференцировку гомологичной ткани или клетки и/или соматической клетки другого гистотипа.3. Композиция по п. 2, где указанная композиция или препарат тотальной РНК, выделенный из интактной лимфоидной клетки или ткани костного мозга здорового донора и/или из донорских лимфоидных клеток или ткани костного мозга здорового донора, подвергнутых активации Т-клеточной популяции, являются регуляторными.4. Композиция по п. 1, где указанная активация Т-клеточной популяции осуществляется in vivo, ex vivo или in vitro.5. Композиция по п. 2, где указанная модуляция гомологичной ткани или клетки и/или соматической клетки другого гистотипа осуществляется ...

СИНТЕТИЧЕСКАЯ ЛЕТАЛЬНОСТЬ И ЛЕЧЕНИЕ РАКА

... 1. Способ лечения субъекта, больного раком с недостатком NMT2, включающий введение упомянутому субъекту ингибитора NMT.2. Способ по п. 1, где упомянутый ингибитор NMT включает ингибитор NMT1.3. Способ по п. 2, где упомянутый ингибитор NMT1 включает небольшую молекулу, антитело, пептидный фрагмент, нуклеиновую кислоту или их комбинации.4. Способ по п. 3, где упомянутая небольшая молекула включает Tris-DBA, НМА или DDD85646, DDD86481 или их производные.5. Способ по п. 3, где упомянутое антитело является моноклональным антителом или поликлональным антителом.6. Способ по п. 3, где упомянутая нуклеиновая иклсота включает молекулу дцРНК (двухцепочечная РНК), молекулу иРНК, молекулу микроРНК, рибозим, молекулу кшРНК (короткая шпилечная РНК) или молекулу миРНК.7. Способ по любому из пп. 1-6, где упомянутый рак представляет собой лимфому, В-клеточную лимфому, фолликулярную лимфому, диффузную В-крупноклеточную лимфому, мантийноклеточную лимфому, В-ХЛЛ/ЛЛ, иммуноцитому/болезнь Вальденстрема, лимфому ...

SLIT-ROBO СИГНАЛИНГ ДЛЯ ДИАГНОСТИКИ И ЛЕЧЕНИЯ ЗАБОЛЕВАНИЯ ПОЧЕК

... 1. Фармацевтическая композиция, содержащая ингибитор ROBO2, который ингибирует биологическую активность ROBO2, характеризующаяся тем, что ингибитор ROBO2 выбран из группы, состоящей из антитела к ROBO2 или его антигенсвязывающего фрагмента, который специфично связывается с ROBO2, антисмысловой молекулы, направленной на нуклеиновую кислоту, кодирующую ROBO2, короткой интерферирующей РНК (siPHK), направленной на нуклеиновую кислоту, кодирующую ROBO2, аптамера РНК или ДНК, который связывается с ROBO2, структурного аналога ROBO2, растворимого белка ROBO2 и ROBO2 ингибиторного полипептида, и фармацевтически приемлемого носителя.2. Фармацевтическая композиция по п. 1, характеризующаяся тем, что ингибитор ROBO2 препятствует или снижает связывание полипептида ROBO2 с SLIT2, с Nck или с обоими.3. Фармацевтическая композиция по любому из пп. 1 или 2, характеризующаяся тем, что ингибитор ROBO2 представляет собой структурный аналог.4. Фармацевтическая композиция по любому из пп. 1 или 2, характеризующаяся ...

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... 1. Способ лечения астмы, осложненной вирусной инфекцией, включающий ! введение страдающему астмой индивидууму эффективного количества олигонуклеотида CpG класса С для лечения астмы, осложненной вирусной инфекцией. ! 2. Способ по п.1, где астма, осложненная вирусной инфекцией, вызвана респираторным вирусом. ! 3. Способ по п.2, где респираторный вирус не является RSV. ! 4. Способ по п.1, где астма, осложненная вирусной инфекцией, вызвана вирусом гриппа. ! 5. Способ по п.1, где индивидуума устанавливает медицинский работник. ! 6. Способ по п.1, где индивидуума устанавливают на основании воздействия фактора риска вирусной инфекции. ! 7. Способ по п.1, где способ включает стадию установления страдающего астмой индивидуума с риском вирусной инфекции. ! 8. Способ по п.1, где олигонуклеотид класса С представляет собой полумягкий олигонуклеотид. ! 9. Способ по п.1, где олигонуклеотид класса С представляет собой SEQ ID NO:10. ! 10. Способ лечения астмы, осложненной вирусной инфекцией, включающий ...

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... 1. Антибактериальный комплекс, содержащий последовательность нуклеиновой кислоты и по меньшей мере одну группу доставки, выбраную из соединений четвертичного амина; бис-аминоалканов и их ненасыщенных производных, при этом амино-компонент аминоалкана является аминогруппой, образующей часть гетероциклического кольца; и антибактериального пептида.2. Антибактериальный комплекс по п.1, отличающийся тем, что группа доставки выбрана из четвертичного производного хинолина или акридина и антибактериального пептида.3. Комплекс по п.1, отличающийся тем, что группой доставки является бис-хинолиний.4. Комплекс по п.1, отличающийся тем, что группой доставки является деквалиний или его аналог.5. Комплекс по п.4, отличающийся тем, что алкиловая цепь аналога деквалиния содержит 8-14 метиловых групп.6. Комплекс по п.5, отличающийся тем, что алкиловая цепь содержит 10 или 12 метиловых групп.7. Комплекс по п.1, отличающийся тем, что соединение четвертичного амина является 10,10'-(декан-1,10-диил)бис(9-амино ...

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ПРИМЕНЕНИЕ СПЕЦИФИЧЕСКОЙ siRNA, НАПРАВЛЕННОЙ ПРОТИВ БЕЛКА S, ДЛЯ ЛЕЧЕНИЯ ГЕМОФИЛИИ

СПОСОБЫ И КОМПОЗИЦИИ ДЛЯ ЛЕЧЕНИЯ ПЕРСИСТИРУЮЩИХ ИНФЕКЦИЙ

... 1. Композиция для смягчения или предотвращения персистирующей инфекции, ангиоиммунобластической лимфомы или нодулярной с лимфоидным преобладанием лимфомы Ходжкина, содержащая ингибитор активности или экспрессии PD-1.2. Композиция по п.1, где указанный ингибитор активности или экспрессии PD-1 понижает экспрессию или активность PD-L1.3. Композиция по п.2, где указанный ингибитор активности или экспрессии PD-1 представляет собой антитело к PD-L1.4. Композиция по п.3, где указанная персистирующая инфекция представляет собой вирус иммунодефицита человека, Т-лимфотрофический вирус человека, вирус герпеса, вирус Эпштейна-Барр или вирус папилломы человека.5. Композиция по п.3, где указанная персистирующая инфекция представляет собой инфекцию вирусом иммунодефицита человека.6. Композиция по п.5, дополнительно содержащая вакцину.7. Композиция по п.6, где указанная вакцина вызывает иммунный ответ в отношении вируса иммунодефицита человека.8. Композиция по п.1, приготовленная для имплантации.9. Композиция ...

КОМПОЗИЦИИ И СПОСОБЫ МОДУЛЯЦИИ SMN2 СПЛАЙСИНГА У СУБЪЕКТА

... 1. Способ, включающий введение субъекту антисмыслового соединения, содержащего антисмысловой олигонуклеотид, комплементарный интрону 7 нуклеиновой кислоты, которая кодирует SMN2 пре-мРНК, где антисмысловое соединение вводится в спинно-мозговую жидкость.2. Способ усиления включения экзона 7 SMN2 мРНК в мотонейронах субъекта, включающий введение субъекту антисмыслового соединения, содержащего антисмысловой олигонуклеотид, комплементарный интрону 7 нуклеиновой кислоты, кодирующей человеческий SMN2, и посредством этого усиление включения экзона 7 SMN2 мРНК в мотонейронах субъекта.3. Способ усиления включения аминокислотной последовательности экзона 7 в SMN2 полипептид в мотонейронах субъекта, включающий введение субъекту антисмыслового соединения, содержащего антисмысловой олигонуклеотид, комплементарный интрону 7 нуклеиновой кислоты, кодирующей человеческий SMN2, и посредством этого усиление включения аминокислотной последовательности экзона 7 в SMN2 полипептид в мотонейронах субъекта.4. Антисмысловое ...

ФАРМАЦЕВТИЧЕСКАЯ КОМБИНАЦИЯ ДЛЯ ЛЕЧЕНИЯ ОПУХОЛИ

... 1. Фармацевтическая комбинация, включающая(a) фармацевтически эффективное количество противоопухолевого средства, выбранного из группы, состоящей из алкилирующего агента, антиметаболита, антибиотика, растительного алкалоида, молекулярнонаправленного лекарственного средства, гормона, платинового комплекса, антисмыслового фактора, антитела и РНКи, и(b) фармацевтически эффективное количество производного жирной кислоты, представленного формулой (I),где L, М и N представляют собой водород, гидрокси, галоген, низший алкил, гидрокси(низший)алкил, низший алканоилокси или оксо, при этом по меньшей мере один из L и М представляет собой группу, отличную от водорода, и пятичленный цикл может иметь по меньшей мере одну двойную связь;А представляет собой -CHили CHOH, -COCHOH, -COOH или соответствующее функциональное производное;В представляет собой простую связь, -CHCH-, -CH=CH-, -C≡C-, -CH-CH-CH-, -CH=CH-CH-, -CH-CH=CH-, -C≡C-CHили -CH-C≡С-;Z представляет собой,,или простую связь,при этом Rи Rпредставляют ...

СПОСОБ ЛЕЧЕНИЯ НЕФРОПАТИИ

СПОСОБЫ ПРИМЕНЕНИЯ АНТАГОНИСТОВ SCD1

... 1. Применение антагониста SCD1 для получения лекарственного средства для лечения злокачественной опухоли, где злокачественная опухоль экспрессирует повышенные уровни одного или нескольких биомаркеров, при котором одним или несколькими биомаркерами является FGFR3, зрелые SREBP1, Δ9-мононенасыщенные жирные кислоты, отношение Δ9-мононенасыщенных жирных кислот к насыщенным жирным кислотам, или один или несколько генов FGFR3-регулированной липогенной сигнатуры.2. Применение по п. 1, при котором злокачественной опухолью является клетка эндометриальной злокачественной опухоли, злокачественная опухоль головы и шеи, злокачественная опухоль почки, злокачественная опухоль яичника, злокачественная опухоль толстой кишки, злокачественная опухоль поджелудочной железы, злокачественная опухоль мочевыводящих путей или злокачественная опухоль мочевого пузыря.3. Применение по п. 2, при котором злокачественной опухолью является злокачественная опухоль почки, злокачественная опухоль поджелудочной железы или ...

КОМПОЗИЦИИ И СПОСОБЫ ДЛЯ САЙЛЕНСИНГА АЛЬДЕГИД-ДЕГИДРОГЕНАЗЫ

... 1. Композиция, содержащая интерферирующую РНК, которая подавляет экспрессию гена альдегид-дегидрогеназы (ALDH), где интерферирующая РНК содержит смысловую цепь и комплементарную антисмысловую цепь, и где интерферирующая РНК содержит двухцепочечный участок длиной от около 15 до около 60 нуклеотидов.2. Композиция по п. 1, где интерферирующая РНК представляет собой двухцепочечную РНК (дцРНК), выбранную из группы, состоящей из миРНК, дцРНК, являющуюся субстратом для Дайсера, кшРНК, аиРНК, пре-микроРНК, и их комбинации.3. Композиция по п. 1, где интерферирующая РНК содержит двухцепочечный участок длиной от около 19 до около 25 нуклеотидов.4. Композиция по п. 1, где интерферирующая РНК химически синтезирована.5. Композиция по п. 1, где интерферирующая РНК содержит 3′-выступающий конец в одной или в обеих цепях интерферирующей РНК.6. Композиция по п. 1, где интерферирующая РНК содержит, по меньшей мере, один модифицированный нуклеотид в двухцепочечном участке.7. Композиция по п. 6, где менее чем ...

МОДУЛЯЦИЯ ЭКСПРЕССИИ TIMP1 И TIMP2

... 1. Молекула нуклеиновой кислоты, причем:(а) указанная молекула нуклеиновой кислоты содержит смысловую и антисмысловую нити;(б) каждая нить молекулы нуклеиновой кислоты независимо содержит от 15 до 49 нуклеотидов в длину;(в) последовательность антисмысловой нити, содержащая в длину от 15 до 49 нуклеотидов, комплементарна последовательности мРНК, кодирующей TIMP1 (SEQ ID NO:1) или TIMP2 (SEQ ID NO:2); и(г) последовательность смысловой нити, содержащая в длину от 15 до 49 нуклеотидов, комплементарна последовательности антисмысловой нити, образуя таким образом участок дуплекса, и содержит состоящую из 15-49 нуклеотидов последовательность мРНК, кодирующую TIMP1 (SEQ ID NO:1) или TIMP2 (SEQ ID NO:2).2. Молекула нуклеиновой кислоты по п.1, отличающаяся тем, что последовательность антисмысловой нити комплементарна последовательности мРНК, кодирующей TIMP1 человека (SEQ ID NO:1), и при этом антисмысловая нить и смысловая нить включают пары последовательностей, выбранных из группы, состоящей из: ...

ЛЕЧЕНИЕ ЗАБОЛЕВАНИЙ, СВЯЗАННЫХ С ФАКТОРОМ РОСТА ФИБРОБЛАСТОВ 21 (FGF21), ПУТЕМ ИНГИБИРОВАНИЯ ПРИРОДНОГО АНТИСМЫСЛОВОГО ТРАНСКРИПТА К FGF21

... 1. Способ модулирования функции и/или экспрессии полинуклеотида фактора роста фибробластов 21 (FGF21) в клетках или тканях пациента in vivo или in vitro, включающий:приведение указанных клеток или тканей в контакт с по меньшей мере одним антисмысловым олигонуклеотидом, составляющим в длину от 5 до 30 нуклеотидов, причем указанный по меньшей мере один олигонуклеотид имеет последовательность, по меньшей мере на 50% идентичную последовательности, обратно комплементарной полинуклеотиду, содержащему от 5 до 30 последовательных нуклеотидов в рамках от 1 до 4246 нуклеотида последовательности SEQ ID NO:2; с модулированием, таким образом, функции и/или экспрессии указанного полинуклеотида фактора роста фибробластов 21 (FGF21) в клетках или тканях пациента in vivo или in vitro.2. Способ модулирования функции и/или экспрессии полинуклеотида фактора роста фибробластов 21 (FGF21) в клетках или тканях пациента in vivo или in vitro, включающий:приведение указанных клеток или тканей в контакт с по меньшей ...

СПОСОБЫ ЛЕЧЕНИЯ ИНФЕКЦИИ ГЕПАТИТА В

КОМПОЗИЦИИ И СПОСОБЫ МОДУЛИРОВАНИЯ ЭКСПРЕССИИ HBV И TTR

ЭМУЛЬСИИ ТИПА "МАСЛО В ВОДЕ", КОТОРЫЕ СОДЕРЖАТ НУКЛЕИНОВЫЕ КИСЛОТЫ

... 1. Иммуногенная катионная эмульсия типа «масло в воде», включающая эмульсионные частицы, содержащие масляную сердцевину и катионный липид, и молекулу нуклеиновой кислоты, образующую комплекс с эмульсионными частицами, где средний диаметр эмульсионных частиц составляет приблизительно от 80 нм до 180 нм, а отношение N/P в этой эмульсии составляет по меньшей мере 4:1, при условии, что указанная молекула нуклеиновой кислоты не кодирует секретированную щелочную фосфатазу, и при условии, что указанная молекула нуклеиновой кислоты не является молекулой РНК, кодируемой плазмидой A317, последовательность которой представлена на фигуре 7A заявки на патент США № 61/361892.2. Иммуногенная катионная эмульсия типа «масло в воде» по п. 1, где указанная молекула нуклеиновой кислоты кодирует антиген.3. Иммуногенная катионная эмульсия типа «масло в воде» по п. 1, где указанной молекулой нуклеиновой кислоты является РНК.4. Иммуногенная катионная эмульсия типа «масло в воде» по п. 3, где указанной РНК является ...

КОМПОЗИЦИЯ НОСИТЕЛЯ ДЛЯ СВОЕВРЕМЕННОЙ ДОСТАВКИ НУКЛЕИНОВЫХ КИСЛОТ

... 1. Композиция носителя для доставки нуклеиновой кислоты, содержащая (А) диацилфосфатидилхолин, (В) по меньшей мере один компонент, выбранный из группы, состоящей из холестерина и его производных, и (С) алифатический первичный амин. ! 2. Композиция носителя для доставки нуклеиновой кислоты по п.1, в которой компонент (А) представляет собой диацилфосфатидилхолин, в котором ацильная группа содержит от 4 до 23 атомов углерода. ! 3. Композиция носителя для доставки нуклеиновой кислоты по п.1 или 2, в которой компонент (В) представляет собой холестерин. !4. Композиция носителя для доставки нуклеиновой кислоты по п.1, в которой компонент (С) представляет собой алкиламин, содержащий от 10 до 20 атомов углерода. ! 5. Композиция носителя для доставки нуклеиновой кислоты по п.1, в которой компонент (А) представляет собой, по меньшей мере, один компонент, выбранный из группы, состоящей из димиристоилфосфатидилхолина, дипальмитоилфосфатидилхолина и дистеароилфосфатидилхолина, компонент (В) представляет ...

МОДУЛЯЦИЯ ЭКСПРЕССИИ ФАКТОРА 11

... 1. Соединение, включающее модифицированный олигонуклеотид, состоящий из 12-30 связанных нуклеозидов, нацеленное на нуклеиновую кислоту фактора 11, в котором нуклеотидная последовательность модифицированного олигонуклеотида по меньшей мере на 90% комплементарна части последовательности нуклеиновой кислоты фактора 11, имеющей такую же длину, где необязательно указанная нуклеиновая кислота фактора 11 представляет собой нуклеиновую кислоту фактора 11, представленную в SEQ ID NO: 1 или SEQ ID NO: 2.2. Соединение по п. 1, в котором модифицированный олигонуклеотид включает нуклеотдную последовательность, включающую часть по меньшей мере из 8 смежных нуклеотидных оснований, которая комплементарна имеющей такую же длину части:(i) нуклеотидных оснований 675-704 в SEQ ID NO: 1,(ii) нуклеотидных оснований 1062-1090 в SEQ ID NO: 1,(iii) нуклеотидных оснований 656-676 в SEQ ID NO: 1,(iv) нуклеотидных оснований 665-687 в SEQ ID NO: 1,(v) нуклеотидных оснований 738-762 в SEQ ID NO: 1,(vi) нуклеотидных ...

BEHANDLUNG DES HARNBLASENKREBSES DURCH MYCOBACTERIUM PHLEI ZELLWAND

Use of marker sequences for the diagnosis of rheumatoid arthritis, where the marker sequences of a complementary DNA (cDNA) from the specific sequence is determined in a patient

Use of marker sequences for the diagnosis of rheumatoid arthritis, is claimed, where at least a marker sequence of a complementary DNA (cDNA) from the SEQ ID NO. 1-488 (not defined) or a protein obtained from the sequence, a partial sequence or a fragment of the sequence, is determined in a patient. Independent claims are included for: (1) diagnosing rheumatoid arthritis comprising introducing the marker sequences on a solid carrier and contacting with body fluids or tissue extracts of a patient and determining the interaction of the body fluids or tissue extracts with the marker sequences; (2) a procedure for the stratification, preferably for risk stratification or for the therapy control of a patient with rheumatoid arthritis, comprising determining the marker sequences in a patient; (3) an arrangement of marker sequences; (4) an assay, protein biochip consisting of the arrangement, where the marker sequences are applied on a solid carrier; (5) a diagnostic agent for the diagnosis of ...

Use of marker sequences for the diagnosis of rheumatoid arthritis, where the marker sequences of a complementary DNA (cDNA) from the specific sequence is determined in a patient

Use of marker sequences for the diagnosis of rheumatoid arthritis, is claimed, where at least a marker sequence of a complementary DNA (cDNA) from the SEQ ID NO. 1-488 (not defined) or a protein obtained from the sequence, a partial sequence or a fragment of the sequence, is determined in a patient. Independent claims are included for: (1) diagnosing rheumatoid arthritis comprising introducing the marker sequences on a solid carrier and contacting with body fluids or tissue extracts of a patient and determining the interaction of the body fluids or tissue extracts with the marker sequences; (2) a procedure for the stratification, preferably for risk stratification or for the therapy control of a patient with rheumatoid arthritis, comprising determining the marker sequences in a patient; (3) an arrangement of marker sequences; (4) an assay, protein biochip consisting of the arrangement, where the marker sequences are applied on a solid carrier; (5) a diagnostic agent for the diagnosis of ...

Method of screening for agents to treat alzheimer's disease

Stem cell product

Ketone body inhibitors and uses thereof

Materials and methods for modulation of tendon healing

Methods of inducing tissue regeneration

Means and methods for the treatment of pathological angiogenesis

Novel lipids and compositions for the delivery of therapeutics

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structures: (Formula (I) or (XXXV)).

Tyrosine kinase receptor tyro3 as a therapeutic target in the treatment of cancer

The present invention concerns new methods for treating cancer by using TYRO3 inhibitors and methods for identifying new molecules of interest for treating cancer.

Treatment of dystrophin family related diseases by inhibition of natural antisense transcript to dmd family

The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Dystrophin family, in particular, by targeting natural antisense polynucleotides of Dystrophin family. The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of DMD family.

Sensitizing agents for cancer therapy, methods of use and methods for the identification thereof

There is provided herein methods, compounds and methods for identifying compounds, for sensitizing a subject with cancer to a cancer therapy by inhibiting or down-regulating UROD.

Novel lipids and compositions for the delivery of therapeutics

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structure:

Peptide/particle delivery systems

Polymeric nanoparticles, microparticles, and gels for delivering cargo, e.g., a therapeutic agent, such as a peptide, to a target, e.g., a cell, and their use for treating diseases, including angiogenesis-dependent diseases, such as age-related macular degeneration and cancer, are disclosed. Methods for formulating, stabilizing, and administering single peptides or combinations of peptides via polymeric particle and gel delivery systems also are disclosed.

Anti-cancer agent, method for inducing apoptosis of cancer cells, and method for screening for anti-cancer agent

Disclosed is an anti-cancer agent which can inhibit the progression of cell cycle in the M phase, unlike taxane anti-cancer agents. The anti-cancer agent comprises a compound capable of inhibiting specifically the expression and/or functions of RBM8A depicted in SEQ ID NO: 1, Magoh depicted in SEQ ID NO: 3 or an isoform thereof. The anti-cancer agent can inhibit the expression and/or functions of RBM8A or Magoh in cancer cells to terminate the cell cycle in the M phase, thereby inhibiting the proliferation of the cells. Therefore, the anti-cancer agent can inhibit the proliferation of cancer cells and induce the apoptosis of cancer cells, leading to the cure of cancer.

Nucleic acid ligands to ll37

The present invention is directed to nucleic acid ligands to LL37, methods for producing said nucleic acid ligands, and methods for utilizing said nucleic acid ligands. In one exemplary embodiment, for example, this invention relates to nucleic acid ligands exhibiting high specific binding affinity to LL37 peptides, precursors and/or portions thereof. Further, the nucleic acid ligands may bind competitively with native ligands of LL37 and may also inhibit and/or interfere with LL37 function, such as by binding to LL37.

METHODS AND COMPOSITIONS FOR REDUCING TARGET GENE EXPRESSION USING COCKTAILS OF siRNAS OR CONSTRUCTS EXPRESSING siRNAS

The present invention concerns methods and compositions involving the production or generation of siRNA mixtures or pools capable of triggering RNA-mediated interference (RNAi) in a cell. Compositions of the invention include kits that include reagents for producing or generating siRNA pools. The present invention further concerns methods using polypeptides with RNase III activity for generating siRNA mixtures or pools that effect RNAi, including the generation of a number of RNA molecules to the same target gene.

Transcriptome Transfer Produces Cellular Phenotype Conversion

The present invention includes methods for effecting phenotype conversion in a cell by transfecting the cell with phenotype-converting nucleic acid. Expression of the nucleic acids results in a phenotype conversion in the transfected cell. Preferably the phenotype-converting nucleic acid is a transcriptome, and more preferably an mRNA transcriptome.

dsRNA For Treating Viral Infection

The invention relates to double-stranded ribonucleic acids (dsRNAs) targeting gene expression of phosphatidylinositol 4-kinase (PI4K), in particular human phosphatidylinositol 4-kinase, catalytic, beta polypeptide (PIK4CB) or human phosphatidylinositol 4-kinase, catalytic, alpha polypeptide (PIK4CA), and their use for treating infection by positive stranded RNA viruses such as hepatitis C virus (HCV). Each dsRNA comprises an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the PIK4CB or PIK4CA target mRNA. A plurality of such dsRNA may be employed to provide therapeutic benefit. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier, and including a delivery modality such as fully encapsulated liposomes or lipid complexes. The invention further includes methods for treating diseases caused by positive stranded RNA virus infection using the pharmaceutical compositions; and methods for inhibiting the propogation of positive stranded RNA viruses in and between cells.

Detection and treatment of autoimmune disorders

Disclosed herein are methods of treatment of autoimmune diseases such as systemic lupus erythematosus (SLE) as well as clinical assays for detection of autoimmune disease activity in patients utilizing a PD1 ligand.

Carbohydrate conjugates as delivery agents for oligonucleotides

The present invention provides iRNA agents comprising at least one subunit of the formula (I): wherein: A and B are each independently for each occurrence O, N(R N ) or S; X and Y are each independently for each occurrence H, OH, a hydroxyl protecting group, a phosphate group, a phosphodiester group, an activated phosphate group, an activated phosphite group, a phosphoramidite, a solid support, —P(Z′)(Z″)O-nucleoside, —P(Z′)(Z″)O-oligonucleotide, a lipid, a PEG, a steroid, a lipophile, a polymer, —P(Z′)(Z″)O-Linker-OP(Z′″)(Z″″)O-oligonucleotide, a nucleotide, an oligonucleotide, —P(Z′)(Z″)-formula (I), —P(Z′)(Z″)— or -Linker-R; R is L G , -Linker-L G , or has the structure shown below: L G is independently for each occurrence a carbohydrate, e.g., monosaccharide, disaccharide, trisaccharide, tetrasaccharide, oligosaccharide, polysaccharide; R N is independently for each occurrence H, methyl, ethyl, propyl, isopropyl, butyl, or benzyl; and Z′, Z″, Z′″ and Z″″ are each independently for each occurrence O or S.

Use of DR6 and p75 Antagonists to Promote Survival of Cells of the Nervous System

The present invention relates to Death Receptor-6 (DR6) proteins which are members of the tumor necrosis factor (TNF) receptor family, and have now been shown to be important for regulating apoptosis in cells of the nervous system. In addition, it has been discovered that p75 is a ligand for DR6. As a result, this invention relates to methods for inhibiting the interaction of DR6 and p75 using DR6 and/or p75 antagonists. In addition, the methods described herein include methods of promoting survival of cells of the nervous system using DR6 antagonists, optionally in combination with p75 antagonists, and methods of treating neurodegenerative conditions by the administration of a DR6 antagonists, optionally in combination with a p75 antagonist.

Use of pkc isozymes for diagnosis and treatment of neuroblastoma

The present invention pertains to the use of PKC-epsilon (PKC-ε), PKC-delta (PKC-δ), PKC-eta, and/or PKC-theta as biomarker(s) for prediction and/or detection of neuroblastoma, as well as therapeutic targets for treatment of neuroblastoma.

In Vivo Polynucleotide Delivery Conjugates Having Enzyme Sensitive Linkages

The present invention is directed compositions for delivery of RNA interference (RNAi) polynucleotides to cells in vivo. The compositions comprise amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or DPC) are further covalently linked to an RNAi polynucleotide or co-administered with a targeted RNAi polynucleotide-targeting molecule conjugate.

Process for the identification of compounds for treating cancer

Process for the identification of compounds for treating cancer. The invention relates to a method for identifying candidate compounds for use as therapeutic agents for the treatment of cancer, among those who are able to activate the MDA-5 protein or increase NOXA protein levels and to trigger autophagy. It is based on the fact that activation of dsRNA sensor MDA-5 is able to trigger the destruction of cancer cells by activation both autophagy and apoptosis, autonomously and selectively in tumor cells, without provoking the stabilization of the natural antagonist NOXA, MCL-1. The invention also relates to the use of double-stranded RNAs of the same or similar nature such as polyinosinic-polycytidylic acid (pIC), complexed with carriers such as polyethylenimine polycation (PEI), for the manufacture of medicines for the treatment of cancer.

Hydrogels used to deliver medicaments to the eye for the treatment of posterior segment diseases

This invention provides a polymeric drug delivery system including a hydrogel containing one or more drugs for the treatment of a posterior segment disease. Allowing passive transference of this drug from a dilute solution into the hydrogel produces the delivery system. The hydrogel, when placed in contact with the eye, delivers the drug. The delivery of the drug is sustained over an extended period of time, which is of particular utility in the eye, which is periodically flushed with tears. This sustained delivery accelerates the treatment process while avoiding potential damaging effects of localized delivery of high concentrations of compounds, e.g., from eye drops.

Diagnostic and Therapeutic Uses for B Cell Maturation Antigen

Biomarkers and therapies against autoimmune diseases, including systemic lupus erythematosus (SLE) are described herein. The present invention is based on the discovery of B cell maturation antigen (BCMA) and BCMA variant expression on SLE monocytes that can be directly associated with disease activity. The findings of the present invention enable the design of monoclonal antibodies or recombinant proteins that can block BCMA and BCMA variants as well as BCMA-bound APRIL.

Modified L-Nucleic Acid

A modified L-nucleic acid, containing an L-nucleic acid part conjugated to a non-L-nucleic acid part is described. The conjugate has extended retention time in and demonstrates a delayed elimination from an organism.

Modified double-stranded polynucleotide

The present invention provides a double-stranded polynucleotide having a sense strand polynucleotide consisting of a nucleotide sequence complementary to a target sequence in a target gene, and an antisense strand polynucleotide having a nucleotide sequence complementary to the sense strand polynucleotide, wherein an aryl or heteroaryl compound is bound to a phosphate group at the 5′-end of the antisense strand polynucleotide.

Compositions and methods for modulating circadian synchronization

The present invention relates to a modulator of glucocorticoid biosynthesis, degradation and/or receptor activation for use in preventing or treating symptoms and/or diseases associated with jet lag. The compositions of the invention may be used as a lead compound for developing a drug for preventing or treating symptoms and/or diseases associated with jet lag. The invention relates to the discovery that administration of the modulator(s) to a subject results in a directional change of the time point of maximum amounts of glucocorticoids in the subject as compared to the time point of maximum amounts of glucocorticoids in a subject not treated with the modulator(s).

Tusc2 therapies

A method for predicting a subject's response to a TUSC2 therapy is provided. In particular, a subject's response is predicted based on the proportion of cancers cells that are apoptotic. Also provided is a method of treating a subject previously predicted to have a favorable response with a TUSC2 therapy. Methods for treating cancer by administration of a TUSC2 therapeutic in conjunction with an EGFR inhibitor and/or a protein kinase inhibitor are also disclosed. Kits and reagents for use in TUSC2 therapy are provided.

Compositions for Controlling Varroa Mites in Bees

An isolated nucleic acid agent is disclosed comprising a nucleic acid sequence which downregulates expression of a gene product of a Varroa destructor mite. Compositions comprising same and uses thereof are also disclosed.

Inhibitors of Atypical Protein Kinase C and Their Use in Treating Hedgehog Pathway-Dependent Cancers

Methods and compositions are provided for modulating Hedgehog (Hh) pathway signaling in a cell. Aspects of the methods include methods for inhibiting Hh pathway-promoted cancer proliferation and/or metastasis that is promoted by Hh pathway signaling, methods for treating cancers promoted by Hh pathway signaling, and methods for screening candidate agents for the ability to treat a cancer promoted by Hh pathway signaling. In addition, reagents and kits thereof that find use in practicing the subject methods are provided.

Novel Lipids and Compositions for Intracellular Delivery of Biologically Active Compounds

The present invention provides novel amino-lipids, compositions comprising such amino-lipids and methods of producing them. In addition, lipid nanoparticles comprising the novel amino-lipids and a biologically active compound are provided, as well as methods of production and their use for intracellular drug delivery.

Conjugates, particles, compositions, and related methods

Particles and conjugates for delivering nucleic acid agents. Compositions containing the particles, the conjugates, or both. Methods of using the particles, the conjugates, and the compositions.

Treatment of pancreatic developmental gene related diseases by inhibition of natural antisense transcript to a pancreatic developmental gene

The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of a Pancreatic Developmental gene, in particular, by targeting natural antisense polynucleotides of a Pancreatic Developmental gene. The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of Pancreatic Developmental genes.

Therapeutic Applications Targeting SARM1

The present disclosure provides methods for reducing axonal and/or synaptic degradation in neurons by modulating sterile α/Armadillo/Toll-Interleukin receptor homology domain protein (SARM) activity and/or expression.

Therapeutic agent for fibroid lung

Disclosed are: a substance transfer carrier to an extracellular matrix-producing cell in the lung, which comprises a retinoid; a therapeutic agent for fibroid lung, which utilized the carrier; and a preparation kit of the therapeutic agent.

Compositions and Methods for Inhibiting Gene Expression of Hepatitis B Virus

The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a Hepatitis B Virus gene. The invention also relates to a pharmaceutical composition comprising the dsRNA or nucleic acid molecules or vectors encoding the same together with a pharmaceutically acceptable carrier; methods for treating diseases caused by Hepatitis B Virus infection using said pharmaceutical composition; and methods for inhibiting the expression of a Hepatitis B Virus gene in a cell.

Mitochondrial enhancement of cells

Certain embodiments disclosed herein include, but are not limited to, at least one of compositions, methods, devices, systems, kits, or products regarding rejuvenation or preservation of stem cells. Certain embodiments disclosed herein include, but are not limited to, methods of modifying stem cells, or methods of administering modified stem cells to at least one biological tissue.

Lipid formulated dsrna targeting the pcsk9 gene

This invention relates to composition and methods using lipid formulated siRNA targeted to a PCSK9 gene.

Methods of Inducing Tissue Regeneration

Methods are provided for producing cells within a lineage (lineage restricted cells) from post-mitotic differentiated cells of the same lineage ex vivo and in vivo, and for treating a subject in need of tissue regeneration therapy by employing these lineage-restricted cells. In addition, the production of lineage restricted cells from postmitotic tissues derived from patients with diseases allows for a characterization of pathways that have gone awry in these diseases and for screening of drugs that will ameliorate or correct the defects as a means of novel drug discovery. Also provided are kits for performing these methods.

Novel cationic lipids and methods of use thereof

The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel cationic lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of a specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

CATIONIC LIPIDS

The invention provides a cationic lipid comprising: 2. The cationic lipid of wherein the at least one amino acid is an α-amino acid.3. The cationic lipid of wherein the side chain of the at least one amino acid is an optionally substituted alkylene chain.4. The cationic lipid of wherein the cationic moiety or cationic precursor of the at least one amino acid is or comprises an amine claim 1 , amidine or guanidine group claim 1 , or a protonated amine claim 1 , amidine or guanidine group.5. The cationic lipid of wherein the at least one amino acid is a basic amino acid.6. The cationic lipid of wherein the basic amino acid is arginine claim 5 , lysine claim 5 , histidine or ornithine.7. The cationic lipid of wherein the basic amino acid is arginine.81. The cationic lipid of wherein the head group comprises two or more amino acids.9. The cationic lipid of wherein the head group comprises from two to four amino acids.10. The cationic lipid of wherein each of the amino acids in the headgroup is the same.11. The cationic lipid of wherein the head group is represented by formula (1):{'br': None, 'sup': 2', '1, 'sub': n', '2, '—[(N(H)—C(H)(R)—C(═O)]—N(R)\u2003\u2003(1)'} [{'sup': '1', 'sub': '1-5', 'each Ris independently hydrogen or a Calkyl;'}, 'n is from 1 to 10; and', {'sup': '2', 'each Ris independently the side chain of an α-amino acid.'}], 'wherein12. The cationic lipid of wherein the two lipophilic moieties are independently of formula (8):{'br': None, 'sup': '6', 'R—C(O)\u2003\u2003(8),'} {'sup': '6', 'Rrepresents a saturated or unsaturated fatty alkyl chain, optionally comprising fused cyclic regions whereby to form a polycyclic hydrocarbyl moiety.'}, 'wherein14. The cationic lipid of claim 12 , wherein R—C(O)— is represented as CH(CH)C(═O)— wherein q is from 5 to 100 claim 12 , more usually 10 to 30 claim 12 , for example 12 to 24 claim 12 , optionally wherein one or more non-adjacent pairs of methylene groups (i.e. CHCHunits) are each replaced with CH═CH units ...

RETINOID-LIPOSOMES FOR TREATING FIBROSIS

What is described are pharmaceutical compositions comprising a double-stranded nucleic acid molecule comprising a sense strand and an antisense strand wherein the sense and antisense strands are selected from the oligonucleotides described as SERPINH1_2 (SEQ ID NOS: 60 and 127), SERPINH1_45a (SEQ ID NOS: 98 and 165), and SERPINH1_51 (SEQ ID NOS: 101 and 168), and drug carrier comprising a mixture of a retinoid and a lipid vesicle, and methods of using these pharmaceutical compositions to treat a disease associated with hsp47 expression, including fibrosis. 1. A pharmaceutical composition comprising a drug carrier and a double-stranded nucleic acid molecule , wherein the drug carrier comprises a liposome and a stellate cell-specific amount of a retinoid , wherein the liposome comprises a bilayer of lipid molecules , and wherein the double-stranded nucleic acid molecule comprises the structure:{'br': None, 'sub': 'x', '5′ (N)—Z 3′ (antisense strand)'}{'br': None, 'sub': 'y', '3′ Z′—(N′)-z″ 5′ (sense strand)'}wherein each of N and N′ is a nucleotide which may be unmodified or modified, or an unconventional moiety;{'sub': x', 'y, 'wherein each of (N)and (N′)is an oligonucleotide in which each consecutive N or N′ is joined to the next N or N′ by a covalent bond;'}wherein each of Z and Z′ is independently present or absent, but if present independently includes 1-5 consecutive nucleotides or non-nucleotide moieties or a combination thereof covalently attached at the 3′-terminus of the strand in which it is present;{'sub': 'y', 'wherein z″ may be present or absent, but if present is a capping moiety covalently attached at the 5′-terminus of (N′);'}wherein each of x and y is independently an integer between 18 and 40;{'sub': y', 'x, 'wherein the sequence of (N′)has complementary to the sequence of (N); and'}{'sub': 'x', 'wherein (N)includes an antisense sequence to the mRNA coding sequence for human hsp47 exemplified by SEQ ID NO:1; wherein the composition prevents or ...

Treatment of methionine sulfoxide reductase a (msra) related diseases by inhibition of natural antisense transcript to msra

The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Methionine Sulfoxide Reductase A (MSRA), in particular, by targeting natural antisense polynucleotides of Methionine Sulfoxide Reductase A (MSRA). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of MSRA.

Cancer-specific genetic rearrangements

The present invention relates to the field of cancer. More specifically, the present invention provides compositions and methods useful for treating cancer characterized by the expression of mutant FAM190A proteins. In a specific embodiment, a method for treating a patient having a cancer characterized by a FAM190A intragenic rearrangement comprises the step of administering to the patient an agent that inhibits a biological function or reduces the level or expression of the FAM190A protein.

USP47 Inhibtors and Methods to Induce Apoptosis

The present invention relates to USP47 (ubiquitin specific protease 47) inhibitors and methods for inducing apoptosis or cell death in a target cell. In certain embodiments, the invention relates to methods and kits to screen for related agents that induce apoptosis. Additionally, the invention relates to assays for screening compounds capable of acting as USP47 inhibitors. 1. A method of inducing apoptosis or cell death comprising contacting a target cell with an effective amount of an inhibitor of ubiquitin specific protease 47 (USP47).2. The method of claim 1 , wherein the target cell is a diseased or abnormal cell from tissue or a cell that exhibits a disease or abnormal condition selected from the group consisting of cancer claim 1 , infection claim 1 , immune disorder claim 1 , cardiovascular disease claim 1 , and inflammatory disorders.3. The method of claim 1 , further comprising contacting the cell with a second agent for sensitizing the cell to DNA damage or apoptosis.4. A method of killing a target cell comprising contacting the cell with an effective amount of an inhibitor of ubiquitin specific protease 47 (USP47).5. The method of claim 4 , further comprising contacting the cell with a second agent for sensitizing the cell to DNA damage.6. The method of claim 4 , wherein the target cell is a diseased or abnormal cell from tissue or a cell that exhibits a disease or abnormal condition selected from the group consisting of cancer claim 4 , infection claim 4 , immune disorder claim 4 , cardiovascular disease claim 4 , and inflammatory disorders.711-. (canceled)12. A method of treating cancer comprising administering an effective amount of a ubiquitin specific protease 47 (USP47) inhibitor to a subject suffering from cancer.13. The method of claim 12 , wherein the USP47 inhibitor induces apoptosis.14. The method of claim 12 , wherein the USP47 inhibitor results in loss of beta-transducin repeat containing protein (β-TrCP) activity.15. A kit for screening for ...

Methods and Compositions for Reducing Interleukin-4 or Interleukin-13 Signaling

The present invention relates generally to methods and compositions for reducing Interleukin-4 or Interleukin-13 signaling, in particular to treat asthma and atopic dermatitis. The inventors have found that Rac/PAK mediated endocytosis of the ligand bound type I (IL-4R with the chains IL-4Ra and IL-2-Rg) and/or type II receptor (IL-13R with the chains IL-4Ra and IL-13Ra1) is needed for the IL-4 and/or IL-13 mediated activation of downstream signalling events including phosphorylation of Stat family transcrition factors. These discoveries enable new methods of screening compounds that modulate Interleukin-4 and Interleukin-13 signalling, as well as new methods for treating conditions characterized by increased Interleukin-4 and Interleukin-13 levels. These conditions include inflammatory conditions, asthma bronchiale, atopic dermatitis, allergies, atopic syndromes, allergic rhinitis, and th2-induced conditions. 1. A method for reducing Interleukin-4 or Interleukin-13 signaling in a cell or subject comprising administering an inhibitor of Rac/Pak driven endocytosis in an amount sufficient to reduce or inhibit endocytosis of IL-4R or IL-13R.2. The method of claim 1 , wherein said inhibitor of Rac/Pak driven endocytosis is administered in amount effective to reduce or inhibit phosphorylation of Stat family transcription factors.3. The method of claim 1 , wherein the inhibitor of Rac/Pak driven endocytosis is selected from agents inhibiting Rac-1 or Pak1/2.5. The method of claim 4 , wherein said peptide inhibiting Rac-1 is N17Rac.6. The method of claim 4 , wherein said peptide inhibiting PAK1 comprises amino acids 83-149 of PAK1.7. A method of treating a condition characterized by increased Interleukin-4 or Interleukin-13 levels in a subject in need thereof comprising administering an inhibitor of Rac/Pak driven endocytosis in a therapeutically effective amount.8. The method of claim 7 , wherein the inhibitor of Rac/Pak driven endocytosis is selected from agents ...

TREATING CANCER BY MODULATING MAMMALIAN STERILE 20-LIKE KINASE 3

The present invention relates to a method for modulating miRNA, said method being characterized in that a modulator of XRN1 is used. Also provided are uses of said method for therapeutical purposes, reagents therefore, as well as screening methods. 1. A method for modulating miRNA in a sample , said method being characterized in that the sample is contacted with a modulator of XRN1.2. (canceled)3. The method of claim 16 , wherein the method is performed to treat a disease and wherein a therapeutically effective amount of said modulator of XRN1 is administered to said subject.4. The method of claim 3 , wherein the disease is a cancer claim 3 , a metabolic disease claim 3 , a developmental disorder claim 3 , a cardiac disease or a viral infection.5. The method of claim 16 , wherein the modulator of XRN1 is a small molecule claim 16 , for instancc a RNasc inhibitor.6. The method of claim 16 , wherein the modulator of XRN1 is an antibody.7. The method of claim 16 , wherein the modulator of XRN1 is an agonist.8. The method of claim 16 , wherein the modulator of XRN1 is an inhibitor of XRN1.9. The method of wherein said inhibitor of XRN1 decreases or silences the expression of XRN1.10. The method of wherein the inhibitor is a siRNA.11. The method of claim 16 , wherein the subject is a mammal.12. (canceled)13. (canceled)14. A method for the identification of a substance that modulates the expression of XRN1 and/or its biological activity claim 16 , which method comprises the steps of:(i) contacting a XRN1 polypeptide or a fragment thereof having the biological activity of XRN1, a polynucleotide encoding such a polypeptide or polypeptide fragment, an expression vector comprising such a polynucleotide or a cell comprising such an expression vector, and a test substance under conditions that in the absence of the test substance would permit XRN1 expression and/or biological activity; and(ii) determining the amount of expression and/or biological activity of XRN1, e.g. the ...

MicroRNA-130a,b as a Tumor Suppressor and Sensitizing Agent for Chemotherapy

The present invention provides a method of improving a therapeutic response to a cancer treatment, in a subject, the method comprising administering an effective amount of an agent that enhances the expression of microRNA-130 or an agent that mimics the effects of microRNA-130. Further provided is a method of treating a cancer in a subject in need of such treatment comprising the step of administering an effective amount of a microRNA-130 or an agent that enhances the expression of microRNA-130. 1. A method of providing a prognosis for ovarian cancer in a subject , comprising the steps of:obtaining a biological sample from said subject; andtesting said biological sample to determine whether or not microRNA-130 is under-expressed in said sample, relative to the expression of microRNA-130 in a control sample, whereby the under-expression of microRNA-130 in said biological sample indicates that a tumor in said subject is resistant to a chemotherapy.2. A method of improving a therapeutic response to a cancer treatment , in a subject , the method comprising administering an effective amount of an agent that enhances the expression of microRNA-130 or an agent that mimics the effects of microRNA-130.3. The method of claim 2 , whereby said agent is microRNA-130a or microRNA-130b.4. The method of claim 2 , whereby said agent is a double-stranded miRNA mimic.5. The method of claim 2 , whereby said agent is an oligonucleotide based pre-microRNA-130 drug.6. The method of claim 2 , whereby said cancer is selected from the group consisting of lung cancer claim 2 , pancreatic cancer claim 2 , skin cancer claim 2 , hematological neoplasms claim 2 , breast cancer claim 2 , brain cancer claim 2 , colon cancer claim 2 , follicular lymphoma claim 2 , bladder cancer claim 2 , cervical cancer claim 2 , endometrial cancer claim 2 , esophageal cancer claim 2 , gastric cancer claim 2 , head and neck cancer claim 2 , multiple myeloma claim 2 , liver cancer claim 2 , lymphomas claim 2 , oral ...

APOPTOSIS INDUCER FOR CANCER CELL

The present invention revealed that by suppressing the expression of the WRN gene, the BLM gene, or the RecQ1 gene, which belong to the RecQ helicase family, apoptosis is induced in various cancer cells and their proliferation is suppressed. Compounds that suppress the expression of RecQ helicase family genes or the functions of RecQ helicase proteins are thought to have the activity of inducing apoptosis. 1. A method for inducing apoptosis of cancer cells comprising a step of administering a compound that suppresses the expression of a WRN gene into a subject , wherein the compound induces apoptosis in cancer cells but does not induce apoptosis in normal cells.2. The method according to claim 1 , wherein the compound that suppresses the expression of the WRN gene is a double-stranded RNA having RNAi activity towards the WRN gene.3. The method according to claim 2 , wherein the double-stranded RNA comprises a sense RNA comprising a sequence homologous to an arbitrary 20 to 30 consecutive nucleotides from the mRNA of the WRN gene claim 2 , and an antisense RNA claim 2 , comprising the sequence complementary to the sense RNA.4. The method according to claim 2 , wherein either strand of the double-strand RNA with RNAi activity comprises the nucleotide sequence of any one of SEQ ID NOs: 2 claim 2 , 35 claim 2 , 36 claim 2 , and 53-62. The Sequence Listing associated with this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into the specification. The name of the text file containing the Sequence Listing 390081401D1_SEQUENCE_LISTING.txt. The text file is 163 KB, was created on Sep. 27, 2012, and is being submitted electronically via EFS-Web.The present invention relates to apoptosis inducers for cancer cells, which comprise as an active ingredient a compound that suppresses the expression of a gene belonging to the RecQ DNA helicase family, or a compound that suppresses the function of the protein encoded by that ...

Hyaluronic Acid Decomposition-Promoting Factor and Inhibitor Thereof

The present invention is directed to KIAA1199, which is a novel factor involved in decomposition of hyaluronic acid, and to use thereof. More specifically, the invention is directed to a hyaluronic acid decomposition-promoting agent containing the KIAA1199 gene and a protein encoded by the gene; to a hyaluronic acid decomposition-inhibiting agent characterized by inhibiting the activity or expression thereof (including an siRNA or a monoclonal antibody); and to a method for screening a novel hyaluronic acid decomposition-controlling agent, in which the method contains employing the expression of KIAA1199 as an index. 1. A method for screening a hyaluronic acid decomposition-controlling agent , wherein the method comprises assessing a hyaluronic acid decomposition controlling effect of a test substance by use of cells in which a KIAA1199 gene is highly expressed transiently or stably.2. The method according to claim 1 , wherein the hyaluronic acid decomposition controlling effect of the test substance is assessed on the basis of the expression level of the KIAA1199 gene or a protein encoded by the KIAA1199 gene as an index.3. The method according to claim 1 , which comprises the following steps:1) culturing cells in the presence or absence of the test substance;2) determining the expression level of the KIAA1199 gene or a protein encoded by the KIAA1199 gene in the cells; and3) assessing the hyaluronic acid decomposition controlling effect of the test substance on the basis of the difference between the expression level of the KIAA1199 gene or the protein encoded by the KIAA1199 gene in the cells determined in the presence of the test substance and that determined in the absence of the test substance.4. The method according to claim 1 , which comprises the following steps:1) culturing cells in coexistence with a labeled hyaluronic acid in the presence or absence of the test substance;2) recovering a culture supernatant after culturing, and determining a molecular ...

THERAPEUTIC USES OF INHIBITORS OF RTP801

The present invention provides novel molecules, compositions, methods and uses for treating microvascular disorders, eye diseases and respiratory conditions based upon inhibition of the RTP801 gene and/or protein. 128-. (canceled)29. A double-stranded compound comprising a sense strand and an antisense strand wherein the sense strand comprises ribonucleotides , the sequence of which is set forth in SEQ ID NO:16 and the antisense strand comprises ribonucleotides , the sequence of which is set forth in SEQ ID NO:66;wherein each ribonucleotide in the sense strand and in the antisense strand is independently unmodified or modified; andwherein each ribonucleotide is bound to each adjacent ribonucleotide by a covalent bond.31. The compound of claim 30 , wherein at least one A claim 30 , C claim 30 , G claim 30 , or U is a sugar-modified ribonucleotide.32. The compound of claim 31 , wherein in the sugar-modified ribonucleotide a 2′ OH group is replaced by —H claim 31 , —OCH claim 31 , —OCHCH claim 31 , —OCHCHCHor —NH.33. The compound of claim 32 , wherein the 2′OH group is replaced by —OCH).34. The compound of claim 30 , wherein at least one A claim 30 , C claim 30 , G or U is a ribonucleotide modified in its base.35. The compound of claim 29 , wherein at least one covalent bond comprises a phosphorothioate bond.36. A method of treating a patient suffering from a disorder associated with elevated expression of RTP801 which comprises administering to the patient the compound of in an amount effective to reduce the expression of RTP801 so as to thereby treat the patient.37. The method of claim 36 , wherein the disorder is a respiratory disorder claim 36 , an eye disease claim 36 , a microvascular disorder claim 36 , or a spinal cord injury.39. The compound of claim 38 , wherein x=y=19.40. The compound of claim 38 , wherein at least one A claim 38 , C claim 38 , G claim 38 , or U comprises a sugar-modified ribonucleotide.41. The compound of claim 40 , wherein in the sugar- ...

Compositions and Methods for Reduced Scarring and for Treatment of Fibrosis

Methods of treating, reducing or preventing fibrosis or scarring including administering a therapeutic molecular agent selected from the group consisting of an agent that inhibits chaperonin containing Tcomplex polypeptide subunit eta polypeptide (“CCT-eta”), an agent that inhibits a-Smooth Muscle Actin (“a-SMA”), or a combination thereof, are presented. The fibrosis may include Dupuytren's contracture, Peyronie's disease, pulmonary fibrosis, cirrhosis, interstitial lung disease or scarring alopecia. 1. A method of reducing scarring comprising administering a therapeutic molecular agent selected from an agent that inhibits chaperonin containing T-complex polypeptide subunit eta , an agent that inhibits α-Smooth Muscle Actin , or a combination thereof.2. The method of claim 1 , wherein scarring comprises fibrosis.3. The method of claim 1 , wherein the agent that inhibits CCT-eta is selected from an agent that inhibits expression of CCT-eta mRNA claim 1 , an agent that inhibits CCT-eta protein claim 1 , or a combination thereof.4. The method of claim 3 , wherein the agent that inhibits CCT-eta mRNA comprises an siRNA comprising a sense strand comprising SEQ ID No. 1 or a variant thereof and an antisense strand comprising SEQ ID No. 2 or a variant thereof.5. The method of claim 3 , wherein the agent that inhibits CCT-eta mRNA comprises an siRNA that inhibits a target mRNA selected from SEQ ID No. 7 claim 3 , 11 claim 3 , 12 claim 3 , 13 claim 3 , 14 claim 3 , a variant thereof or a combination thereof.6. The method of claim 3 , wherein the agent that inhibits CCT-eta protein is an antibody.7. The method of claim 6 , wherein the antibody inhibits the CCT-eta protein comprising SEQ ID No. 9 claim 6 , 15 claim 6 , 16 claim 6 , 17 claim 6 , 18 or a combination thereof.8. The method of claim 1 , wherein the agent that inhibits α-SMA is selected from an agent that inhibits expression of α-SMA mRNA claim 1 , an agent that inhibits α-SMA protein claim 1 , or a combination ...

Composition for nucleic acid delivery using metal nanoparticles and preparing method thereof

The present invention relates to a composition for nucleic acid delivery and a method for preparing the same, more particularly to a composition for nucleic acid delivery having excellent stability in the body environment and excellent intracellular delivery efficiency of nucleic acid, and enabling target directed delivery of nucleic acid, and a method for preparing the same.

METHODS OF USING SCD1 ANTAGONISTS

Provided herein are therapies for the treatment of pathological conditions, such as cancer, and method of using SCD1 antagonists. 1) A method of treating a cancer cell in an individual comprising administering to the individual an effective amount of an SCD1 antagonist.2) The method of claim 1 , wherein the cancer cell is an endometrial cancer cell claim 1 , a head and neck cancer cell claim 1 , a kidney cancer cell claim 1 , an ovarian cancer cell claim 1 , a colon cancer claim 1 , a pancreatic cancer cell claim 1 , an urinary cancer cell claim 1 , or a bladder cancer cell.3) The method of claim 2 , wherein the cancer cell is a kidney cancer cell claim 2 , pancreatic cancer cell claim 2 , or bladder cancer cell.4) The method of claim 3 , wherein the cancer cell expresses elevated levels of one or more biomarkers compared to a reference sample claim 3 , reference cell claim 3 , reference tissue claim 3 , control sample claim 3 , control cell claim 3 , control tissue claim 3 , or internal control (e.g. claim 3 , housekeeping gene).5) A method of treating cancer in an individual comprising administering to the individual an effective amount of an SCD1 antagonist.6) The method of claim 5 , wherein the cancer in the individual expresses elevated levels of one or more biomarkers compared to a reference sample claim 5 , reference cell claim 5 , reference tissue claim 5 , control sample claim 5 , control cell claim 5 , control tissue claim 5 , or internal control (e.g. claim 5 , housekeeping gene)7) A method of treating cancer in an individual comprising administering to the individual an effective amount of an SCD1 antagonist claim 5 , wherein treatment is based upon the individual having cancer expressing elevated levels of one or more biomarkers compared to a reference sample claim 5 , reference cell claim 5 , reference tissue claim 5 , control sample claim 5 , control cell claim 5 , control tissue claim 5 , or internal control (e.g. claim 5 , housekeeping gene).8) The ...

Tiki1 and Tiki2, Wnt Inhibitors

This invention relates to Tiki1 and Tiki2 proteins and nucleic acids, cells expressing the same, and methods for identifying compounds that modulate Tiki1/2 activity for use in the treatment of osteoporosis or cellular proliferative disorders.

Peptides useful as cell-penetrating peptides

A peptide having an amino acid sequence containing at least eight consecutive amino acids of the human lactoferrin protein or of the bovine lactoferrin protein. The peptide is suitable as a cell-penetrating peptide. A complex of the peptide and a cargo molecule non-covalently bound to the peptide. The cargo molecule may be a nucleic acid, an amino acid, a peptide, a protein, a carbohydrate, a lipid, or a small molecule. A method of penetrating or transfecting a cell using the complex.

Method for the delivery of oligonucleotides

The invention relates to a method for obtaining formulations which improve the binding capacity of siRNAs in relation to plasma components, which promote the transport of siRNA in the blood, which increase the passage of siRNA through the cell membrane and, consequently, which increase the inhibitory activity of siRNA. The invention also relates to a method for obtaining a formulation comprising siRNA associated with plasma components, characterised in that the method includes a step in which the plasma components are dispersed in an aqueous medium.

METHODS OF LIMITING MICROVASCULAR DAMAGE FOLLOWING ACUTE MYOCARDIAL ISCHEMIA

This disclosure has identified a new ligand-receptor system, proNGF and p75NTR/SorCS2, which is found to be involved in the microvascular functions of the heart. This disclosure provides methods for limiting microvascular damage following acute myocardial ischemia based on administration of an antagonist of this newly identified system, thereby promoting myocardial recovery. 1. A method of limiting microvascular damage following acute myocardial ischemia in a subject , comprising administering to the subject a proNGF antagonist.2. The method of claim 1 , wherein said proNGF antagonist is an antibody specific for proNGF which inhibits the binding of proNGF to p75and/or SorCS2.3. The method of claim 2 , wherein said antibody is an antibody directed to the pro-domain of proNGF.4. The method of claim 1 , wherein said proNGF antagonist is a nucleic acid or peptide aptamer which specifically binds to proNGF and inhibits the binding of proNGF to p75and/or SorCS2.5. The method of claim 1 , wherein said proNGF antagonist is an oligopeptide or small molecule which inhibits the binding of proNGF to p75and/or SorCS2.6. The method of claim 6 , wherein said nucleic acid molecule is an anti-sense molecule or siRNA which reduces the level or activity of proNGF mRNA.7. The method of claim 1 , wherein said proNGF antagonist is administered to the subject within 48 hours of acute myocardial ischemia.8. The method of claim 1 , wherein the proNGF antagonist is administered to the subject via ingestion claim 1 , injection claim 1 , catheter delivery during percutaneous intervention claim 1 , or directly to the heart during open heart surgery.9. A method of limiting microvascular damage following acute myocardial ischemia in a subject claim 1 , comprising administering to the subject a SorCS2 antagonist.10. The method of claim 9 , wherein said SorCS2 antagonist is an antibody directed to SorCS2 which blocks the binding of proNGF to SorCS2.11. The method of claim 10 , wherein said antibody ...

PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF CHLAMYDIAL INFECTION

Subject of the present invention is a pharmaceutical composition comprising at least one inhibitor of a microorganism selected from the family Chlamydiaceae. 142-. (canceled)43. A pharmaceutical composition comprising at least one inhibitor of a microorganism selected from the family Chlamydiaceae , optionally together with pharmaceutically acceptable carriers , adjuvants , diluents or/and additives , wherein the inhibitor is selected from compounds capable of inhibiting the nucleotide metabolism , in particular nucleotide metabolism essential for chlamydial growth , propagation or/and infection.44. The pharmaceutical composition as claimed in claim 43 , wherein inhibition of the nucleotide metabolism includes{'sub': '—', '(a) inhibition of the activity of GMP synthase, in particular GMP synthase EC 6.3.5.2, more particular GMP synthase described by genbank entry NM003875, or'}{'sub': '—', '(b) inhibition of the activity of IMP dehydrogenase 2, in particular IMP dehydrogenase 2 EC 1.1.1.205, more particular IMP dehydrogenase 2 described by genbank entry NM000884.'}45. The pharmaceutical composition as claimed in claim 43 , wherein inhibition comprises inhibition of growth or/and propagation of the microorganism selected from the family Chlamydiaceae.46. The pharmaceutical composition as claimed in claim 43 , wherein inhibition comprises inhibition of the interaction of the microorganism with the host cell.47. The pharmaceutical composition as claimed in claim 43 , wherein inhibition comprises(i) reduction of the number of EB that infected the host cell, or/and(ii) reduction of the number of RB inside the host cell.48. The pharmaceutical composition as claimed in claim 43 , wherein the at least one inhibitor of the microorganism is selected from the group of nucleic acids claim 43 , nucleic acid analogues such as ribozymes claim 43 , peptides claim 43 , polypeptides claim 43 , and antibodies claim 43 , wherein the nucleic acid encodes a GMP synthase or a IMP ...

METHODS AND COMPOSITIONS FOR TREATING CANCER

We describe a method of determining whether a cancer cell is likely to be resistant to treatment by an mTOR inhibitor. The method may comprise detecting PPP2R2B (GenBank Accession Number: NM_18167) in or of the cell. It may, alter-natively, or in addition, comprise detecting PDK1 (GenBank Accession Number: NM_002613), in or of the cell. The method may comprise detecting methylation of the PPP2R2B promoter in or of the cell. It may comprise detecting the expression and/or activity of PPP2R2B in or of the cell. It may comprise detecting PDK1 mediated Myc phosphorylation activity. Methods of choosing a treatment for an individual suffering from or suspected to be suffering from a cancer, determining whether an individual suffering from or suspected to be suffering from a cancer will respond to treatment by an mTOR inhibitor, increasing the sensitivity of a cancer cell to treatment by an mTOR inhibitor, for treating or preventing cancer in an individual suffering or suspected to be suffering from cancer are also provided. We further provide for a combination of an inhibitor of PDK1 expression and/or activity and an mTOR inhibitor for use in a method of treatment or prevention of cancer. 1. A method of determining whether a cancer cell is likely to be resistant to treatment by an mTOR inhibitor , the method comprising detecting: (i) PPP2R2B (GenBank Accession Number: NM181678) or (ii) PDK1 (GenBank Accession Number: NM002613) , or both , in or of the cell.2. A method according to claim 1 , which comprises detecting methylation of the PPP2R2B promoter in or of the cell.3. A method according to claim 1 , which comprises detecting expression and/or activity of PPP2R2B or PDK1 claim 1 , or both claim 1 , in or of the cell.4. A method according to claim 1 , wherein a decreased expression and/or activity of PPP2R2B claim 1 , or an increased expression and/or activity of PDK1 claim 1 , or both claim 1 , compared to a cancer cell that is not mTOR inhibitor resistant claim 1 , ...

Dual Targeted siRNA Therapeutics for Treatment of Diabetic Retinopathy and Other Ocular Neovascularization Diseases

The present invention relates to compositions and methods for treating diabetic retinopathy and other ocular neovascularization diseases. In one embodiment, the composition comprises at least two different siRNA duplexes and a pharmaceutically acceptable carrier. One of the duplexes binds to an mRNA molecule that encodes VEGF, and the other binds to an mRNA molecule that encodes VEGFR2. In another embodiment, the composition further comprises an siRNA duplex that binds to an mRNA molecule that encodes TGFβ1. 1. A composition comprising at least two different siRNA duplexes and a pharmaceutically acceptable carrier , wherein one of said siRNA duplexes binds to an mRNA molecule that encodes VEGF and the other of said siRNA duplexes binds to an mRNA molecule that encodes VEGFR2.2. The composition of further comprising an siRNA duplex that binds to an mRNA molecule that encodes TGFβ1.3. The composition of wherein said siRNA duplexes target both human mRNA and homologous mouse mRNA.4. The composition of wherein said siRNA duplexes target both human mRNA and homologous mouse mRNA.5. The composition of wherein said siRNA duplexes comprise oligonucleotides with a length of 16-27 base pairs.7. The composition of wherein said siRNA duplexes comprise oligonucleotides with a length of 21-25 base pairs.8. The composition of wherein said siRNA duplexes comprises oligonucleotides with a length of 25 base pairs.9. The composition of wherein said siRNA duplexes comprise oligonucleotides with blunt ends at both ends.10. The composition of wherein said siRNA duplexes are selected from the siRNA duplexes listed in Tables 1 and 2.11. The composition of wherein said siRNA duplexes are selected from the siRNA duplexes in Tables 1-3.14. The composition of wherein said duplexes are selected from the group consisting of:a. derived duplexes consisting of 24 contiguous base pairs of any one or more of the duplexes in Tables 1 and 2;b. derived duplexes consisting of 23 contiguous base pairs of ...

Compositions and methods for silencing apolipoprotein b

The present invention provides compositions and methods for the delivery of interfering RNAs such as siRNAs that silence APOB expression in cells such as liver cells. In particular, the nucleic acid-lipid particles provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells such as liver cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of APOB at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

Method for Inhibiting HIV Replication in Mammal and Human Cells

The present invention describes a method to inhibit replication of the human immunodeficiency virus (HIV) by negatively modulating or altering the cytoskeleton, more precisely the proteins forming the intermediate cytoskeletal filaments, wherein the said proteins are vimentin and/or keratin-10. The replication of the virus is inhibited in human cells by intervening in the structure of these proteins. The present invention is also related to the use of agents, which comprise peptides and/or interfering RNA and/or lipidic compounds, said agents producing a negative modulation or alteration of the cytoskeleton to prevent or to treat the HIV infection. The invention provides means and methods for altering the cytoskeleton/filament structure of cells, as a result of which the infection of human cells by HIV is disturbed and can even be completely inhibited. The cytoskeleton is altered by reducing the amount of vimentin and/or keratin (e.g. by transcriptional control using interfering RNA) or by using peptides that disrupt the cytoskeleton. 1. A method to inhibit the replication of the human immunodeficiency virus (HIV) comprising disrupting the structure of cytoskeletal intermediate filaments (IFs) in a mammalian cell.2. The method according to wherein said IFs comprise vimentin and/or keratin proteins.3. The method according to wherein said IFs comprise vimentin and/or keratin-10 proteins.4. The method according to comprising decreasing the amount of vimentin and/or keratin-10 in said IF.5. The method according to comprising decreasing the expression of the genes coding for vimentin and/or keratin-10.6. The method according to wherein the disruption of said IF is achieved by an agent selected from a group consisting of polypeptides claim 1 , peptides claim 1 , nucleic acids and chemical compounds.7. The method according to wherein said agent is a peptide selected from the group of peptides identified as SEQ ID No. 1 to SEQ ID No. 10 claim 6 , and homologues thereof.8. ...

Compositions for inhibiting gene expression and uses thereof

The inventors have examined the means for providing more efficacious miRNA blocking compounds. The inventors have discovered new structural features that surprisingly improve the efficacy of miRNA blocking molecules. These features include the presence of multiple 3′ ends and a linker at the 5′ ends. Surprisingly, these features improve the efficacy of the gene expression blocking compounds in a manner that decreases the compound's biologic instability. Even more surprisingly, this effect has been found to be applicable to both DNA and RNA oligonucleotide-based compounds and to have application in traditional antisense and RNAi technology.

METHOD OF TREATING TUMOR RESISTANT TO HERCEPTIN OR PACLITAXEL USING FOXM1 INHIBITORS AND DETECTING SAME

The invention provides methods of treating cancer, especially breast cancer, and in particular HER2/ErbB2 positive breast cancer using a FoxM1 inhibitor in conjunction with trastuzumab and/or paclitaxel. Pharmaceutical compositions comprising a FoxM1 inhibitor in the presence of trastuzumab and/or paclitaxel are also provided. The invention further provides methods of identifying and treating trastuzumab resistant and/or paclitaxel resistant cancer. Also provided are methods of promoting breast tumor cell differentiation. 196-. (canceled)97. A pharmaceutical composition for inhibiting tumor growth comprising a combination of a FoxM1 inhibitor and trastuzumab or paclitaxel or both trastuzumab and paclitaxel , wherein the combination is in a therapeutically effective amount , and a pharmaceutically acceptable excipient , diluent or carrier.98. The pharmaceutical composition of wherein the combination comprises a FoxM1 inhibitor and trastuzumab and paclitaxel.99. The pharmaceutical composition of wherein the FoxM1 inhibitor comprises an inhibitory P19ARF peptide.100. The pharmaceutical composition of wherein the inhibitory P19ARF peptide comprises a peptide having the sequence of SEQ ID NO:6 or SEQ ID NO:7.101. The pharmaceutical composition of wherein the FoxM1 inhibitor comprises a FoxM1-specific siRNA.102. The pharmaceutical composition of claim 101 , wherein the FoxM1-specific siRNA comprises a polynucleotide having the sequence of SEQ ID NO:8 claim 101 , SEQ ID NO:9 claim 101 , SEQ ID NO:10 claim 101 , or SEQ ID NO:11.103. The pharmaceutical composition of wherein the FoxM1 inhibitor comprises a thiazole antibiotic.104. The pharmaceutical composition of claim 103 , wherein the thiazole antibiotic is siomycin A or thiostrepton.105. The pharmaceutical composition of wherein the FoxM1 inhibitor is an antioxidant.106. The pharmaceutical composition of wherein the antioxidant is N-acetyl-L-cysteine (NAC) claim 105 , catalase claim 105 , 4-Hydroxy-2 claim 105 ,2 claim ...

METHODS AND COMPOSITIONS FOR TREATING PROSTATE CANCER

Treatment of prostate cancer by regional and prolonged release of one or more nucleotide-based RNAi agents is provided. 1. A millimeter-scale drug delivery device (DDD) comprising:A. A biodegradable polymeric matrix; andB. An RNAi (RNA interference) agent that targets a prostate carcinoma-related gene, incorporated within said biodegradable polymeric matrix.2. The DDD of claim 1 , wherein said target is selected from the group consisting of: Androgen Receptor claim 1 , PAPPA pregnancy-associated plasma protein A (Pappalysin) claim 1 , Neurophilin and tolloid-like 2 (NETO2) claim 1 , Protein tyrosine phosphatase receptor a (PTPRA) claim 1 , BMI1 polycomb ring finger oncogene (BMI-1) claim 1 , IL6ST interleukin 6 signal transducer/gp130 claim 1 , Human telomerase reverse transcriptase (hTERT) claim 1 , BRD4 bromodomain containing 4 (BRD4) claim 1 , ErbB3/HER3 claim 1 , PSCA prostate stem cell antigen (PSCA) claim 1 , Enhancer of zeste homolog 2 (EZH2) claim 1 , TMPRSS2/ERG claim 1 , CA12 Carbonic anhydrase XII (CA12) claim 1 , MEK4/MAP2K4 claim 1 , p63/KET claim 1 , Transmembrane and coiled-coil protein 1 (TMCC1) claim 1 , TMCC2 claim 1 , TMCC3 claim 1 , Neurotrimin claim 1 , CD70 claim 1 , Tmem50b claim 1 , Claudin-11 claim 1 , Neuroplastin (NPTN) claim 1 , and CD44.3. The DDD of claim 2 , wherein said target is selected from the group consisting of: Androgen Receptor claim 2 , Pappalysin claim 2 , NETO2 claim 2 , PTPRA claim 2 , BMI-1 claim 2 , IL6ST/gp130 claim 2 , hTERT claim 2 , BRD4 claim 2 , ErbB3/HER3 claim 2 , PSCA claim 2 , and EZH2.4. The DDD of claim 1 , wherein said DDD comprises RNAi agents targeting at least 2 genes selected from the group consisting of: Androgen Receptor claim 1 , Pappalysin claim 1 , NETO2 claim 1 , PTPRA claim 1 , BMI-1 claim 1 , IL6ST/gp130 claim 1 , hTERT claim 1 , BRD4 claim 1 , ErbB3/HER3 claim 1 , PSCA claim 1 , EZH2 claim 1 , TMPRSS2/ERG claim 1 , CA12 claim 1 , MEK4/MAP2K4 claim 1 , p63/KET claim 1 , TMCC1 claim 1 , TMCC2 ...

Therapeutic compositions

This application relates to therapeutic siRNA agents and methods of making and using the agents.

ANTICANCER COMPOSITION

Disclosed is an anticancer composition, comprising an inhibitor against WIG1 and/or YPEL5 or against a protein encoded by the gene. A composition for screening an anticancer agent comprising a nucleic acid having a sequence complementary to an mRNA of WIG1 and/or YPEL5, or an antibody to a protein encoded by the gene is also provided. Also, a method is provided for screening an anticancer agent, which comprises: (A) quantitatively analyzing expression of WIG1 and/or YPEL5 at an mRNA or protein level in a tumor cell which is not treated with a candidate for an anticancer agent; (B) quantitatively analyzing expression of the gene at an mRNA or protein level in a tumor cell after treatment of the candidate for an anticancer agent; and (C) selecting the candidate if the expression level of the gene is increased in step (B), compared to step (A). 1. An anticancer composition , comprising an inhibitor against a gene selected from the group consisting of WIG1 (wild-type p53 induced gene-1) , YPEL5 (yippee-like 5) and a combination thereof , or against a protein encoded by the gene.2. The anticancer composition of claim 1 , wherein the anticancer activity is based on premature senescence in tumor cells.3. The anticancer composition of claim 1 , wherein the gene is an mRNA.4. The anticancer composition of claim 3 , wherein the inhibitor is an siRNA.5. The anticancer composition of claim 4 , wherein the siRNA has the sense sequence of SEQ ID NO: 7 or 9.6. The anticancer composition of claim 1 , wherein the inhibitor against a protein is an antibody.7. A composition for screening an anticancer agent claim 1 , comprising a nucleic acid having a sequence complementary to an mRNA of a gene selected from the group consisting of WIG1(wild-type p53 induced gene-1) claim 1 , YPEL5 (yippee-like 5) and a combination thereof claim 1 , or an antibody to a protein encoded by the gene.8. The composition of claim 7 , wherein the nucleic acid is a DNA complementary to the mRNA.9. The ...

Asymmetric Liposomes for the Highly Efficient Encapsulation of Nucleic Acids and Hydrophilic Anionic Compounds, and Method for Preparing Same

The present invention relates to asymmetric liposomes for high encapsulation efficiency of nucleic acids and hydrophilic anionic compounds, and to a method for preparing same, and specifically, to asymmetric liposomes consisting of a cationic lipid having a small head group as an internal lipid and a neutral or PEGylated lipid having a big head group as an external lipid, wherein nucleic acids and/or anionic compounds are encapsulated in the internal lipid. According to the present invention, asymmetric liposomes, in which nucleic acids and hydrophilic anionic compounds are encapsulated with high efficiency, may be prepared, and thus the same may be used for various purposes, such as gene therapy, and the delivery of hydrophilic anionic drugs which are difficult to prepare as prodrugs, and drug delivery, imaging, etc. can be carried out by encapsulating a fluorescent contrast agent in the liposome. 1. An asymmetric liposome comprising a cationic lipid having a small head group as an internal lipid and a neutral or PEGylated lipid having a big head group as an external lipid , wherein nucleic acids and/or anionic compounds are encapsulated in the internal lipid.2. The asymmetric liposome as set forth in claim 1 , further comprising a function group attached to a surface thereof for cell target-oriented transmission and cell permeation claim 1 ,wherein the function group is antibody or a peptide.3. (canceled)4. The asymmetric liposome as set forth in claim 1 , wherein the internal lipid comprises dioleoyl dimethylammonium-propane (DODAP) and dipalmitoylphosphatidyl ethanolamine (DOPE) or dioleoyl phosphatidylethanolamine (DPPE) claim 1 , in a composition ratio of DODAP:DOPE or DPPE=1:1 to 1:9.5. The asymmetric liposome as set forth in claim 1 , wherein the external lipid comprises a neutral phospholipid claim 1 , a PEGylated phospholipid claim 1 , and cholesterol.6. The asymmetric liposome as set forth in claim 5 , wherein the neutral phospholipid comprises distearoyl ...

COMPOSITIONS AND METHODS FOR TREATING CANCER AND MODULATING STRESS GRANULE FORMATION

The invention provides methods for treating or decreasing the likelihood of developing a stress-granule related disorder and/or cancer by administering one or more poly-ADP-ribose polymerase (PARP) inhibitors, one or more PARP activators, one or more poly-ADP-ribose glycosylase (PARG) activators, and/or one or more poly-ADP-ribose glycohydrolase ARH3 activators. The invention also provides corresponding methods of decreasing stress granule formation and/or proliferation in a cell or a population of cells. The invention further provides methods of increasing the number of stress granules and proliferation in a cell or a population of cells by administering one or more PARP activators, one or more PARP inhibitors, one or more PARG inhibitors, and/or one or more ARH3 inhibitors. The invention also provides methods for screening for agents for treating or decreasing the likelihood of developing a stress granule-related disorder or cancer, and methods for determining the propensity for developing a stress granule-related disorder or cancer, as well as compositions and kits containing one or more PARP inhibitors, one or more PARP activators, one or more PARG activators, and one or more ARH3 activators. 1. A method of treating or decreasing the likelihood of developing a stress granule-related disorder in a subject comprising administering to said subject a therapeutically effective amount of one or more poly-ADP-ribose polymerase (PARP) inhibitor(s) , one or more poly-ADP ribose glycolase (PARG) activators , and/or one or more PARP11 activators.2. The method of claim 1 , wherein said one or more PARP inhibitor(s) selectively decrease the expression and/or one or more activities of one or more PARP(s) selected from the group consisting of PARP5a claim 1 , PARP12 claim 1 , PARP13 isoform 1 (PARP13.1) claim 1 , PARP13 isoform 2 (PARP13.2) claim 1 , and PARP15.3. The method of claim 2 , wherein:(a) said decrease in expression is a decrease in the level of one or more nucleic ...

NOVEL DIAGNOSTIC AND THERAPEUTIC TARGET IN INFLAMMATORY AND/OR CARDIOVASCULAR DISEASES

Methods for diagnosing inflammatory and/or cardiovascular diseases by assaying for Fibroblast Activation Protein (FAP) expression in a body fluid is provided as well as therapeutic means based thereon. 1. A method of determining the presence of an inflammatory and/or cardiovascular disease or condition in a patient comprising assaying(i) a sample of a body fluid taken from said patient for expression of Fibroblast Activation Protein (FAP), wherein expression or an increased expression of said FAP compared to a control sample is indicative for the disease or condition in said patient; and/or(ii) a sample of a thrombus or plaque taken from said patient for expression of FAP, wherein an increased expression of FAP as compared to its expression in a sample of a body fluid taken from said patient is indicative for the disease or condition.2. The method of claim 1 , wherein said body fluid is blood.3. The method of claim 1 , wherein said disease is selected from the group atherosclerosis claim 1 , rheumatoid arthritis claim 1 , stroke or an acute coronary syndrome such as myocardial infarction claim 1 , heart attack claim 1 , chronic liver disease claim 1 , cerebral venous thrombosis claim 1 , deep venous thrombosis or pulmonary embolism.4. The method of claim 2 , wherein the condition is vulnerable atherosclerotic plaques or atherothrombosis.5. The method of claim 1 , comprising assaying said sample for FAP protein or mRNA.6. The method of claim 5 , wherein said assay is an immunoassay.7. The method of claim 6 , wherein said assay is an immunohistochemical assay.8. The method of claim 7 , wherein said assay comprises fluorescence activated cytometry (FACS) claim 7 , indirect ELISA claim 7 , sandwich ELISA or cell culture ELISA.9. The method of claim 6 , wherein said immunoassay comprises contacting said sample with a monoclonal or polyclonal antibody which binds specifically to FAP.10. The method of claim 9 , wherein said monoclonal antibody is a mouse anti-human ...

Methods for inhibition of cell proliferation, synergistic transcription modules and uses thereof

The invention provides for methods for treating nervous system cancers in a subject. The invention further provides methods for treating nervous system tumor cell invasion, migration, proliferation, and angiogenesis associated with nervous system tumors.

INTRACELLULAR DNA RECEPTOR

Provided herein are methods of identifying and using compounds that modulate an AIM2 polypeptide-mediated immune response. Further provided herein are methods of treating disease comprising administering to a patient a compound that decreases expression of an AIM2 polypeptide. Further provided herein are methods of providing gene therapy to a patient comprising administering to the patient a gene therapy agent and a compound that decreases expression of an AIM2 polypeptide. In certain embodiments, a compound that decreases expression of an AIM2 polypeptide comprises an siRNA or an shRNA. 1. A method of treating an autoimmune disease in a patient , comprising administering to the patient a compound that decreases expression of an AIM2 polypeptide.2. The method of claim 1 , wherein the compound comprises an siRNA or an shRNA.3. The method of claim 1 , wherein expression of the AIM2 polypeptide is decreased by at least 50%.4. The method of claim 1 , wherein the disease is selected from the group consisting of: rheumatoid arthritis claim 1 , systemic lupus erythematosis claim 1 , scleroderma claim 1 , dermatomyositis claim 1 , and psoriasis.5. A method of treating an infection comprising administering to a patient a compound that decreases expression of an AIM2 polypeptide.6. The method of claim 5 , wherein the compound comprises an siRNA or an shRNA.7. The method of claim 5 , wherein expression of the AIM2 polypeptide is decreased by 50%.8. The method of claim 5 , wherein the infection is caused by a bacterial pathogen.9ShigellaFrancisellaChlamyidaListeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium leprae, Mycobacterium avium intracellulare, BrucellaSalmonellaLegionella,Rickettsia.. The method of claim 8 , wherein the bacterial pathogen is selected from the group consisting of spp. claim 8 , spp. spp. spp. claim 8 , spp. claim 8 , and10. The method of claim 5 , wherein the infection is caused by a viral pathogen.11. The method of claim 10 , wherein the ...

REGULATORS OF NFAT AND/OR STORE-OPERATED CALCIUM ENTRY

Embodiments of the inventions relate to modulating NFAT activity, modulating store-operated Ca entry into a cell and treating and/or preventing hyperactivity or inappropriate immune response by inhibiting the expression or activities of proteins involved in the calcineurin/NFAT axis. 1. A method of modulating NFAT activity in a subject in need thereof , the method comprising administering a therapeutically effective amount of a pharmaceutical composition comprising an agent that inhibits the activity a protein and/or the expression of a gene identified in Table 4.2. The method of claim 1 , wherein the modulation of NFAT activity comprises increasing the immune response in a subject in need thereof.3. The method of claim 2 , wherein the subject is suffering from an immunodeficiency disorder selected from a group consisting of HIV (human immunodeficiency virus) and AIDS (acquired immunodeficiency syndrome) claim 2 , X-linked agammaglobulinemia claim 2 , selective IgA deficiency claim 2 , Wiskott-Aldrich syndrome claim 2 , chronic granulomatous disease claim 2 , leukocyte adhesion defects claim 2 , Bruton disease claim 2 , kidney failure claim 2 , and combined immunodeficiency disease.4. The method of claim 1 , wherein the subject is suffering from a cell proliferation disease or disorder.5. The method of claim 4 , wherein the cell proliferation disease or disorder is a neoplastic cell proliferation disorder.6. The method of claim 4 , wherein the neoplastic cell proliferation disorder is a therapy resistant cancer claim 4 , a metastasis or malignant cancer.7. The method of claim 1 , wherein the subject is suffering from a cardiovascular disorder.8. The method of claim 7 , wherein the cardiovascular disorders is cardiac hypertrophy claim 7 , restenosis claim 7 , atherosclerosis claim 7 , or angiogenesis.9. The method of claim 1 , wherein the subject is suffering from a bone disease associated with excessive osteoclast formation and the excessive activity needs to be ...

Antibody-Based Depletion of Antigen-Presenting Cells and Dendritic Cells

Disclosed herein are methods and compositions comprising anti-CD74 and/or anti-HLA-DR antibodies for treatment of GVHD and other immune dysfunction diseases. In preferred embodiments, the anti-CD74 and/or anti-HLA-DR antibodies are effective to deplete antigen-presenting cells, such as dendritic cells. Most preferably, administration of the therapeutic compositions depletes all subsets of APCs, including mDCs, pDCs, B cells and monocytes, without significant depletion of T cells. In alternative embodiments, administration of the therapeutic compositions suppresses proliferation of allo-reactive T cells, while preserving cytomegalovirus (CMV)-specific, CD8 memory T cells. The compositions and methods provide a novel conditioning regimen for preventing aGVHD and/or treating chronic GVHD, without altering preexisting anti-viral immunity. 1. A method of killing antigen-presenting cells or dendritic cells comprising:a. exposing the antigen-presenting cell or dendritic cell to an anti-HLA-DR and/or anti-CD74 antibody or antigen-binding fragment thereof; andb. killing the antigen-presenting cell or dendritic cell.2. The method of claim 1 , wherein the anti-CD74 antibody or fragment thereof competes for binding to CD74 with claim 1 , or binds to the same epitope of CD74 as claim 1 , a murine LL1 antibody comprising the light chain CDR sequences CDR1 (RSSQSLVHRNGNTYLH; SEQ ID NO:1) claim 1 , CDR2 (TVSNRFS; SEQ ID NO:2) claim 1 , and CDR3 (SQSSHVPPT; SEQ ID NO:3) and the heavy chain variable region CDR sequences CDR1 (NYGVN; SEQ ID NO:4) claim 1 , CDR2 (WINPNTGEPTFDDDFKG; SEQ ID NO:5) claim 1 , and CDR3 (SRGKNEAWFAY; SEQ ID NO:6).3. The method of claim 1 , wherein the anti-CD74 antibody or fragment thereof comprises the light chain CDR sequences CDR1 (RSSQSLVHRNGNTYLH; SEQ ID NO:1) claim 1 , CDR2 (TVSNRFS; SEQ ID NO:2) claim 1 , and CDR3 (SQSSHVPPT; SEQ ID NO:3) and the heavy chain variable region CDR sequences CDR1 (NYGVN; SEQ ID NO:4) claim 1 , CDR2 (WINPNTGEPTFDDDFKG; SEQ ...

Method and medicament for inhibiting the expression of a given gene

The invention relates to an isolated RNA that mediates RNA interference of an mRNA to which it corresponds and a method of mediating RNA interference of mRNA of a gene in a cell or organism using the isolated RNA.

Methods And Compositions For Prevention Or Treatment Of RSV Infection

Methods and compositions are provided for the prevention or treatment of RSV infection in a human. The methods include administering one or more doses of a composition comprising an siRNA. The dose can be formulated for topical or parenteral administration. Topical administration includes administration as a nasal spray, or by inhalation of respirable particles or droplets.

RNA Interference Mediated Inhibition of Prolyl Hydroxylase Domain 2 (PHD2) Gene Expression Using Short Interfering Nucleic Acid (siNA)

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond expressed/synthetic to the modulation of PHD2 gene expression and/or activity, and/or modulate a beta-catenin gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short inter-fering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsR-NA), micro-RNA (miRNA), and short hair-pin RNA (shRNA) molecules that are capa-ble of mediating or that mediate RNA inter-ference (RNAi) against PHD2 gene expres-sion. 1. A double-stranded short interfering nucleic acid (siNA) molecule comprising R-008039846-001E , R-008039847-001N , R-008039882-001P , R-008039848-001X , R-008039849-001F , R-008053961-001S , R-008054086-001B , R-008147454-000S or any combination thereof.2. A composition comprising one or more siNA molecules of and a pharmaceutically acceptable carrier or diluent.3. A composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, '(a) one or more siNA molecules of ;'}(b) a cationic lipid;(c) cholesterol;(d) DSPC; and(e) PEG-DMG.4. A composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'one or more siNA molecules of ;'}(b) (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine;(c) cholesterol;(d) DSPC; and(e) PEG-DMG.5. The composition according to claim 4 , wherein the (13Z claim 4 ,16Z)—N claim 4 ,N-dimethyl-3-nonyldocosa-13 claim 4 ,16-dien-1-amine claim 4 , cholesterol claim 4 , DSPC claim 4 , and PEG-DMG have a molar ratio of 50:30:10:2 respectively.6. A composition comprising the composition according to and a pharmaceutically acceptable carrier or diluent.7. A method of treating a human subject suffering from a condition which is mediated by the action claim 1 , or by loss of action claim 1 , of PHD2 claim 1 , which comprises administering to said subject an ...

NCAM-VASE AND NEURODEGENERATION

Inhibitors of NCAM-VASE, compositions comprising said inhibitors, and methods of using said inhibitors for stimulation of neuroplasticity and/or neuroregeneration in the central nervous system, and for increasing neuronal cell response to agents that stimulate neuroplasticity and/or neuroregeneration in the central nervous system, are provided. The inhibitor or composition may be used, for example, for treating brain or spinal cord injury; schizophrenia, motor neurone disease; a neurodegenerative disorder such as Alzheimer's disease, multiple sclerosis or Parkinson's disease; ischaemia caused by stroke; or for improving learning and/or memory. 1. (canceled)2. (canceled)3. The method of wherein the inhibitor is an antisense RNA molecule or an interfering RNA that is capable of causing a reduction of NCAM-VASE mRNA transcription.4. The method of wherein the inhibitor is a soluble polypeptide comprising the Ig4 domain of NCAM-VASE.5. The method of wherein the inhibitor is a soluble polypeptide comprising a further sequence from NCAM-VASE in addition to the Ig4 domain.6. The method of wherein the inhibitor is an antibody or antibody fragment or derivative able to bind selectively to NCAM-VASE.7. The method of claim 12 , wherein the inhibitor is administered in combination with a second agent which promotes neuroplasticity and/or neuroregeneration.8. The method of claim 7 , wherein the second agent is selected from the list consisting of NGF claim 7 , BDNF claim 7 , FGF claim 7 , CNTF claim 7 , GDNF claim 7 , NT3 claim 7 , NT4/5 dbcAMP and forskolin.9. The method of claim 12 , wherein the method is for treating brain or spinal cord injury.10. The method of claim 12 , wherein the method is for treating schizophrenia claim 12 , motor neurone disease claim 12 , for treating a neurodegenerative disorder including Alzheimer's disease claim 12 , multiple sclerosis or Parkinson's disease; for treating ischaemia caused by stroke; or for improving learning and/or memory.11. ( ...

TREATMENT OF ABNORMALITIES OF GLUCOSE METABOLISM WITH AN ANTAGONIST OF INHIBITOR OF DIFFERENTIATION 1

A method of treating or preventing an abnormality of glucose metabolism in a subject, the method comprising administering an antagonist of Inhibitor of Differentiation 1 (Id1) to the subject. 1. A method of treating or preventing an abnormality of glucose metabolism in a subject , the method comprising administering an antagonist of Inhibitor of Differentiation 1 (Id1) to the subject.2. The method according to claim 1 , wherein the subject suffers from a condition selected from the group consisting of type 2 diabetes claim 1 , hyperglycaemia claim 1 , hyperinsulinemia claim 1 , insulin resistance claim 1 , glucose intolerance and combinations thereof.3. The method of claim 1 , wherein the subject suffers from type 2 diabetes.4. The method of claim 1 , wherein the antagonist of Id1 is a small molecule claim 1 , a nucleic acid claim 1 , an antibody or a peptide.5. The method of claim 1 , wherein the antagonist binds to Id1.6. The method of claim 5 , wherein the antagonist is a peptide comprising a sequence set forth in any one or more of SEQ ID NOs: 5-16.11. The method of claim 5 , wherein the antagonist is a small molecule selected from the group consisting of: 1-(4-methoxybenzyl)-4-(2 claim 5 ,4 claim 5 ,5-trimethoxybenzyl)piperazine; N′-acetyl-N′-(3-chloro-4-methylphenyl)-2-hydroxy-2 claim 5 ,2-diphenylacetohydrazide; 6 claim 5 ,7-dimethoxy-2-methyl-1-oxo-3-pyridin-3-yl-N-[3-(trifluoromethyl)phenyl]-1 claim 5 ,2 claim 5 ,3 claim 5 ,4-tetrahydroisoquinoline-4-carboxamide; 2-[3-(3 claim 5 ,4-dimethylphenyl)-2 claim 5 ,4-dioxo-3 claim 5 ,4 claim 5 ,6 claim 5 ,7 claim 5 ,8 claim 5 ,9-hexahydro-2H-cyclohepta[4 claim 5 ,5]thieno[2 claim 5 ,3-d]pyrimidin-1(5H)-yl]-N-(2-methoxyethyl)acetamide; 4-acetyl-N claim 5 ,N-dibutyl-3 claim 5 ,5-dimethyl-1H-pyrrole-2-carboxamide; N-(4-isopropylphenyl)-2-[8-morpholin-4-ylcarbonyl)-11-oxodibenzo[b claim 5 ,f][1 claim 5 ,4]thiazepin-10(11H)-yl]acetamide; ethyl 1-(3-[(2 claim 5 ,5-dimethyloxyphenyl)amino]-3-oxopropyl)-4- ...

Inhibition of LAR Phosphatase to Enhance Therapeutic Angiogenesis

The present invention relates to the regulation of angiogenesis and arteriogenesis by leukocyte antigen-related protein tyrosine phosphatase (LAR). The invention further relates to the use of inhibitors of LAR expression and/or activity to stimulate angiogenesis and/or arteriogenesis. 12-. (canceled)3. A method of increasing angiogenesis and/or arteriogenesis in a tissue of a subject , comprising decreasing the expression and/or activity of LAR in said tissue of said subject.4. A method of treating or preventing ischemia in a tissue of a subject , comprising decreasing the expression and/or activity of LAR in said tissue of said subject.5. The method of claim 3 , wherein said subject has diabetes.6. The method of claim 3 , wherein said subject has cardiovascular or cerebrovascular disease or has experienced ischemia or stroke.7. The method of claim 3 , wherein said subject is at risk for ischemia.8. The method of claim 3 , wherein said subject has a graft or other transplanted tissue claim 3 , anastomosis claim 3 , wound claim 3 , ulcer claim 3 , burn claim 3 , male pattern baldness claim 3 , atherosclerosis claim 3 , ischemic heart tissue claim 3 , ischemic peripheral tissue claim 3 , myocardial or cerebral infarction claim 3 , or vascular occlusion or stenosis.9. The method of claim 3 , comprising delivering an inhibitor of LAR expression and/or activity to said tissue.10. The method of claim 9 , wherein said tissue is in a limb.11. The method of claim 10 , wherein said tissue is in a foot or toe.12. The method of claim 9 , wherein said tissue is in the heart or brain.13. The method of claim 3 , wherein decreasing the expression and/or activity of LAR comprises decreasing the level of a nucleic acid encoding LAR.14. The method of claim 13 , wherein the method comprises delivering an antisense RNA to said subject to decrease the level of a nucleic acid encoding LAR.15. The method of claim 13 , wherein the method comprises delivering an siRNA to said subject to ...

PROSTAGLANDIN TRANSPORTER INHIBITORS

The present invention generally relates to prostaglandin transport. More specifically, the invention is directed to compounds that inhibit prostaglandin transport and subsequent COX-2 induction, and methods relating thereto. 112-. (canceled)1445-. (canceled)46. A method of inhibiting COX-2 in a mammal , the method comprising administering an inhibitor of prostaglandin transporter activity to the mammal.47. The method of claim 46 , wherein the inhibitor is an antisense nucleic acid claim 46 , a ribozyme or an siRNA claim 46 , wherein the antisense nucleic acid claim 46 , the ribozyme or the siRNA is specific for the mRNA of the prostaglandin transporter.48. The method of claim 46 , wherein the inhibitor is an antibody or aptamer that specifically inhibits the prostaglandin transporter.51. The method of claim 49 , wherein R2 comprises a carboxyl or phenol group.52. The method of claim 49 , wherein R2 is a C-Cstraight or branched alkyl claim 49 , a phenyl claim 49 , a fused aryl claim 49 , a fused heteroaryl claim 49 , or any combination thereof claim 49 , optionally substituted with a halogen claim 49 , a carboxyl claim 49 , an amino claim 49 , a nitro claim 49 , a SCH claim 49 , a hydroxyl claim 49 , a C-Calkoxy claim 49 , C-Cstraight or branched alkyl claim 49 , an azido claim 49 , or a combination thereof.53. The method of claim 49 , wherein R2 is a C-Cstraight or branched alkyl claim 49 , a phenyl claim 49 , a fused aryl claim 49 , or a combination of a C-Cstraight or branched alkyl and a phenyl claim 49 , optionally substituted with a halogen claim 49 , one or more hydroxyls claim 49 , a methoxy claim 49 , a nitro claim 49 , a carboxy claim 49 , or a combination thereof.56. The method of claim 46 , wherein the mammal is a human suffering from a disease or disorder at least partially mediated by a cyclooxygenase-2.57. The method of claim 56 , wherein the disease or disorder involves pain and/or inflammation.58. The method of claim 56 , wherein the disease or ...

METHOD FOR PRONGF ASSAY FOR IN VITRO DIAGNOSIS OF CANCER IN PARTICULAR BREAST, THYROID OR LUNG CANCER AND THERAPEUTIC USE OF PRONGF

A ProNGF inhibitor for preparing a drug, said drug being in particular useful for blocking remote dissemination and cell invasion in patients suffering from cancer, in particular breast, thyroid or lung cancer. 1. A method for treatment of a patient suffering from cancer , comprising administering a therapeutically effective amount of a ProNGF inhibitor to said patient.2. The method as claimed in claim 1 , wherein the amount is effective for blocking cell migration or invasion in patients suffering from cancer.3. The method as claimed in claim 1 , wherein the ProNGF inhibitor is an anti-ProNGF antibody or a ProNGF receptor analog in soluble form.4. The method as claimed in claim 1 , wherein said ProNGF inhibitor is able to specifically penetrate into cells of interest.5. The method as claimed in claim 1 , wherein the ProNGF inhibitor is an siRNA of a ProNGF receptor.6. A method of blocking cancerous cell migration claim 1 , comprising administering an effective amount of a ProNGF inhibitor to a person claim 1 , thereby blocking migration of cancer cells.7. A pharmaceutical composition claim 1 , comprising claim 1 , as an active ingredient claim 1 , at least one ProNGF inhibitor in combination with a pharmaceutually acceptable excipient.8. A pharmaceutical composition as claimed in claim 7 , wherein the ProNGF inhibitor is an anti-ProNGF antibody or a ProNGF receptor analog in soluable form.9. A pharmaceutical composition as claimed in claim 7 , wherein the ProNGF inhibitor is an siRNA of a ProNGF receptor.10. A pharmaceutical composition as claimed in claim 7 , wherein said ProNGF inhibitor is able to specifically penetrate into cells of interest. This is a Continuation of application Ser. No. 13/137,101 filed Jul. 20, 2011, which is a Division of application Ser. No. 12/087,606 filed Jul. 10, 2008, which in turn is a National Phase of PCT/FR2007/050708, filed Jan. 30, 2007. The disclosures of the prior applications are hereby incorporated by reference herein in ...

Drug carrier and drug carrier kit for inhibiting fibrosis

Disclosed is a stellate cell-specific drug carrier comprising a stellate cell-specific amount of a retinoid derivative and/or a vitamin A analogue, and a drug carrier component other than the retinoid derivative and/or a vitamin A analogue. Also disclosed in a medicine comprising the stellate cell-specific drug carrier, and a drug in an amount effective for controlling the activity or growth of stellate cells.

Method for selective oligonucleotide modification

Method for producing a modified oligonucleotide, wherein at least one polymer, preferably polyalkylene oxide, and/or a compound is covalently bound to the 5′-end or the 3′-end of the oligonucleotide via native ligation forming a native ligation site, with the proviso that the polymer and/or the compound is not a protein or peptide, if only the 5′-end of the oligonucleotide is modified by binding of the polymer or compound via native ligation. The invention is further directed to a modified oligonucleotide obtainable by the inventive method as well as the use of such modified oligonucleotide for the preparation of a medicament for preventing and/or treating a tumor, formation of metastasis, an immune disease or disorder, a cardiovascular disease or disorder, and/or a viral disease or disorder.

Selective inhibition of polyglutamine protein expression

The present invention relates to the selective inhibition of protein expression of CAG repeat-related disease proteins such as Huntingtin Disease Protein and Ataxin-3 using double-stranded RNAs and nucleic acid analogs. Chemically-modified RNAs having at least one mismatch as compared to the target CAG repeat sequence are specifically contemplated.

COMPOSITION FOR REGENERATING NORMAL TISSUE FROM FIBROTIC TISSUE

The present invention relates to a pharmaceutical composition and a method for regenerating normal tissue from fibrotic tissue, the pharmaceutical composition and the method employing a collagen-reducing substance. In accordance with the present invention, normal tissue can be therapeutically regenerated from fibrotic tissue. 1. A pharmaceutical composition comprising a collagen-reducing substance in an amount effective for regenerating normal tissue from fibrotic tissue.2. The pharmaceutical composition according to claim 1 , wherein the collagen-reducing substance is selected from the group consisting of a suppressor of collagen production by collagen-producing cells claim 1 , a promoter of collagen decomposition claim 1 , and a suppressor of a collagen decomposition inhibitor.3. The pharmaceutical composition according to claim 1 , wherein it further comprises a targeting agent for collagen-producing cells in fibrotic tissue.4. The pharmaceutical composition according to claim 3 , wherein the targeting agent is a retinoid.51. The pharmaceutical composition according to Claim claim 3 , wherein the fibrotic tissue continually receives a fibrotic stimulus.6. The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is for regenerating normal tissue from fibrotic tissue in a space for the growth and differentiation of stem cells claim 1 , the space being formed by a reduction of collagen accumulated in the fibrotic tissue.7. The pharmaceutical composition according to claim 2 , wherein the suppressor of collagen production by collagen-producing cells is selected from the group consisting of a TGFβ inhibitor claim 2 , HGF or a substance promoting the production thereof claim 2 , a PPARγ ligand claim 2 , an angiotensin inhibitor claim 2 , a PDGF inhibitor claim 2 , relaxin or a substance promoting the production thereof claim 2 , a substance that inhibits the production and secretion of an extracellular matrix component claim 2 , a ...

Mirna expression in allergic disease

Disclosed are methods for detecting an allergic lung disease that involve assessing the level of one or more microRNAs (miRNAs) in a biological sample, wherein the level of the one or more miRNAs in the biological sample compared to a reference level of the one or more miRNAs is indicative of allergic lung disease. Also disclosed are methods for the treatment or prevention of inflammatory or allergic lung disease that involve administration of a let-7 miRNA inhibitor as set forth herein, as well as biochips and kits that can be applied in the methods of the present invention.

POTENTIATOR OF ACTIVITY OF ANTI-CANCER AGENT AND USE THEREOF, AND BIOMARKER FOR PREDICTION OF PROGNOSIS IN CANCER PATIENT AND USE THEREOF

Disclosed is a means for improving the clinical outcomes of cancer therapy. Specifically disclosed is an activity potentiator comprising a compound capable of inhibiting the expression of RFP (RET finger protein) gene or the activity of RFP as an active ingredient. The activity of an anti-cancer agent having an oxidative stress inducing ability can be potentiated by using the anti-cancer agent in combination with the activity potentiator. Further specifically disclosed are a biomarker useful for the recognition of prognosis in a cancer patient and use of the biomarker. 115-. (canceled)16. An action enhancing agent of an anticancer drug having an oxidative stress-inducing ability , comprising a compound , as an active ingredient , for suppressing expression of a RFP (RET finger protein) gene or action of RFP.17. The action enhancing agent according to claim 16 , wherein the compound is selected from the group consisting of the following (a) to (d):(a) siRNA targeting the RFP gene;(b) a nucleic acid construct for generating the siRNA targeting the RFP gene in a cell;(c) an antisense nucleic acid targeting a transcriptional product of the RFP gene; and(d) a ribozyme targeting a transcriptional product of the RFP gene.18. The action enhancing agent according to claim 16 , which is used in combination with an anticancer drug having an oxidative stress-inducing ability.19. A method for enhancing action of an anticancer drug having an oxidative stress-inducing ability claim 16 , the method comprising a step of suppressing expression of a RFP gene or action of RFP in a target cell.20. A method for treating a cancer claim 16 , the method comprising:{'claim-ref': {'@idref': 'CLM-00016', 'claim 16'}, 'a step of administering the action enhancing agent according to ; and'}a step of administering an anticancer drug having an oxidative stress-inducing ability.21. A method for testing resistance to an anticancer drug claim 16 , the method comprising:a step of examining an ...

Methods and compositons for cell-proliferation-related disorders

Methods of treating and evaluating subjects having neoactive mutants of IDH (e.g., IDH1 or IDH2).

TREATMENT OF ABNORMAL OR EXCESSIVE SCARS

Methods and compositions comprising combinations and uses of a first anti-connexin agent and a second anti-connexin agent, for example, one or more anti-connexin polynucleotides and one or more anti-connexin peptides or peptidomimetics, are provided for the treatmen or prevention of abnormal or excessive scarring. 1. A method of treating a subject having or at risk for developing an abnormal or excessive scar , comprising administering to the subject a composition comprising therapeutically effective amounts of an anti-connexin peptide.2. A method of claim 1 , wherein said peptide comprises a sequence selected from SEQ.ID.NOS:15 to 23.3. A method of claim 1 , wherein said peptide comprises said anti-connexin 43 peptide or anti-connexin 43 peptidomimetic.4. A method according to claim 3 , wherein the composition comprises about 0.01 to about 100 milligrams of said anti-connexin 43 peptide or anti-connexin 43 peptidomimetic.5. A method of treating a subject having or at risk for developing an abnormal or excessive scar claim 3 , comprising administering to the subject a composition comprising therapeutically effective amounts of a first anti-connexin agent and a second anti-connexin agent claim 3 , wherein said first agent is an anti-connexin polynucleotide and said second agent is an anti-connexin peptide or peptidomimetic.6. A method according to claim 5 , wherein said polynucleotide is an antisense polynucleotide.7. A method according to claim 6 , wherein said antisense polynucleotide comprises a sequence selected from SEQ.ID.NOS:1 to 12.8. A method according to claim 6 , wherein said antisense polynucleotide is selected from: GTA ATT GCG GCA AGA AGA ATT GTT TCT GTC (SEQ ID NO:1); GTA ATT GCG GCA GGA GGA ATT GTT TCT GTC (SEQ ID NO:2); and claim 6 , GGC AAG AGA CAC CAA AGA CAC TAC CAG CAT (SEQ ID NO:3).9. A method according to claim 6 , wherein said antisense polynucleotide has from about 15 to about 35 nucleotides and is sufficiently complementary to connexin 43 ...

Ligand-conjugated monomers

This invention relates composition and methods for making and using chemically modified oligonucleotides agents for inhibiting gene expression.

COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF MUTANT EGFR GENE

The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a mutant Epidermal Growth Factor Receptor (EGFR), and methods of using the dsRNA to inhibit expression of mutant EGFR. 1. A double-stranded ribonucleic acid (dsRNA) , wherein said dsRNA comprises at least two sequences that are complementary to each other and wherein a sense strand comprises a first sequence and an antisense strand comprises a second sequence comprising a region of complementarity which is substantially complementary to at least a part of a mRNA encoding an delta-Epidermal Growth Factor Receptor (deltaEGFR) , and wherein said region of complementarity is less than 30 nucleotides in length.2. The dsRNA of claim 1 , wherein said dsRNA comprises at least one modified nucleotide.3. The dsRNA of claim 2 , wherein at least one of said modified nucleotides is chosen from the group of: a 2′-O-methyl modified nucleotide claim 2 , a nucleotide comprising a 5′-phosphorothioate group claim 2 , and a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group.4. The dsRNA of claim 2 , wherein said modified nucleotide is chosen from the group of: a T-deoxy-2′-fluoro modified nucleotide claim 2 , a 2′-deoxy-modified nucleotide claim 2 , a locked nucleotide claim 2 , an abasic nucleotide claim 2 , 2′-amino-modified nucleotide claim 2 , 2′-alkyl-modified nucleotide claim 2 , morpholino nucleotide claim 2 , a phosphoramidate claim 2 , and a non-natural base comprising nucleotide.5. The dsRNA of claim 1 , wherein the region of complementary is at least 15 nucleotides in length.6. The dsRNA of claim 1 , wherein the region of complementarity is between 19 and 21 nucleotides in length.7. The dsRNA of claim 1 , wherein the dsRNA comprises a sense strand consisting of a sense strand sequence selected from Tables 2 and 3 claim 1 , and an antisense strand consisting of an antisense sequence selected from Tables 2 and 3.8. The dsRNA of claim 1 , wherein the sense ...

Compositions and methods for inducing cancer cell death

Described herein are pharmaceutical compositions including a sugar or mannose analog (e.g., 2-DG) and an inhibitor of at least one of PERK and GCN2 (e.g., an inhibitor of PERK and an inhibitor of GCN2) for treating cancer, and methods of treating cancer in a subject involving administration of these pharmaceutical compositions. Pharmaceutical compositions [or inducing death of cancer cells include a therapeutically effective amount of a pharmaceutical composition including: a pharmaceutically acceptable carrier, a sugar analog in an amount effective for inhibiting the growth of cancer cells, and an inhibitor of at least one of: PERK and GCN2 in an amount effective for blocking phosphorylation of eif2-1″t in the cancer cells, wherein the combined amounts of the sugar analog and the inhibitor of at least one of: PERK and GCN2 are sufficient for inducing death of the cancer cells.

COMPOSITIONS AND METHODS FOR INHIBITION OF OR TREATMENT OF DENGUE VIRUS INFECTION

The present invention relates to a method of interfering with dengue infection comprising interfering with dengue virus binding to a syndecan present on a cell targeted by dengue virus. The present invention further relates to treating a patient for dengue virus infection comprising administering to a patient, either having a dengue infection or a patient exposed to dengue infection, an effective amount of an agent that interferes with dengue virus binding to a syndecan on a surface of a cell targeted by dengue virus. The present invention further relates to a pharmaceutical composition comprising a pharmaceutically acceptable carrier, and an effective amount of an agent that interferes with dengue virus binding to a syndecan on a surface of a cell targeted by dengue virus. 1. A method of interfering with dengue virus infection comprising:interfering with dengue virus binding to syndecan-2, syndecan-4, or both, present on a cell targeted by dengue virus.2. The method according to claim 1 , wherein said interfering is carried out with an antibody specific to syndecan-2 claim 1 , syndecan-4 claim 1 , or a combination thereof.3. The method according to claim 2 , wherein the antibody is a polyclonal antibody claim 2 , monoclonal antibody claim 2 , or active fragment thereof.4. (canceled)5. The method according to claim 1 , wherein said interfering is carried out with heparin or heparan sulfate.6. The method according to claim 1 , wherein said interfering is carried out by introducing an RNAi into the cell to inhibit expression of syndecan-2 claim 1 , syndecan-4 claim 1 , or a combination thereof.7. (canceled)8. The method according to claim 1 , wherein the dengue virus is contacted with a soluble extracellular domain of syndecan-2 claim 1 , syndecan-4 claim 1 , or a combination thereof.9. (canceled)10. The method according to claim 1 , wherein a small molecule inhibitor of syndecan-2 claim 1 , and/or syndecan-4 is used.11. The method according to claim 1 , wherein the ...

METHOD FOR PREDICTING THE RESPONSIVENESS TO CHEMOTHERAPY

The present invention concerns a method for predicting the responsiveness of an individual suffering from leukemia to a chemotherapeutic drug. In particular, this method comprises determining the proportion of leukemic cells expressing cytoplasmic PCNA in a biological sample of the individual. The present invention also relates to a tyrosine kinase inhibitor for use for the treatment of an individual suffering from leukemia and having a proportion of leukemic cells expressing cytoplasmic PCNA in a biological sample lower than a predetermined threshold. The invention also pertains to a method for diagnosing whether an individual suffers, or is at risk of suffering, from leukemia. 1. A method for predicting the responsiveness of an individual suffering from leukemia to a chemotherapeutic drug , said method comprising determining the proportion of leukemic cells expressing cytoplasmic PCNA in a biological sample of the individual.2. The method of claim 1 , wherein a proportion of leukemic cells expressing cytoplasmic PCNA higher than a predetermined threshold is indicative that the individual is likely not to respond to the chemotherapeutic drug.3. The method of claim 1 , wherein a proportion of leukemic cells expressing cytoplasmic PCNA of at least 50% is indicative that the individual is likely not to respond to the chemotherapeutic drug.4. The method of claim 1 , wherein the chemotherapeutic drug is selected from the group consisting of alkaloids claim 1 , alkylating agents claim 1 , antimetabolites claim 1 , antibiotics claim 1 , tyrosine kinase inhibitors claim 1 , topoisomerase inhibitors claim 1 , monoclonal antibodies claim 1 , biological response modifiers and corticosteroids.5. The method of claim 1 , wherein the chemotherapeutic drug is a tyrosine kinase inhibitor or a topoisomerase inhibitor.6. The method of claim 1 , wherein the chemotherapeutic drug is imatinib mesilate or doxorubicin.7. The method of claim 1 , wherein the leukemia is a myelocytic ...

INHIBITORS OF LONG AND VERY LONG CHAIN FATTY ACID METABOLISM AS BROAD SPECTRUM ANTI-VIRALS

The present invention provides methods and compounds for treating viral infections using modulators of host cell enzymes relating to long chain fatty acid and lipid droplet metabolism. It includes a method of treating viral infections using triacsin C and its relatives, analogues and derivatives as well as other inhibitors of long chain fatty acid metabolism and lipid droplet metabolism. 181-. (canceled)82. A method of treating or preventing viral infection in a mammal , comprising administering to a mammalian subject in need thereof a therapeutically effective amount of an agent that inhibits a long chain fatty acid synthesis enzyme.83. The method of claim 82 , wherein the enzyme is an elongase.84. The method of claim 82 , wherein the enzyme is selected from the group consisting of:i) acyl-CoA synthetase long-chain family member 1 (ACSL1)ii) elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 2 (ELOVL2),iii) elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 3 (ELOVL3),iv) elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 6 (ELOVL6), andv) solute carrier family 27 (fatty acid transporter), member 3 (SLC27A3).85. The method of claim 82 , wherein the agent is an inhibitory polynucleotide.86. The method of claim 82 , wherein the agent is a small molecule.96. The method of claim 82 , wherein the virus is an enveloped virus.97. The method of claim 82 , wherein the virus is human cytomegalovirus (HCMV) claim 82 , hepatitis C virus (HCV) claim 82 , herpes simplex virus (HSV) claim 82 , hepatitis B virus (HBV) claim 82 , Human immunodeficiency virus (HIV) claim 82 , or influenza virus.981. The method of claim claim 82 , wherein the virus is HCMV claim 82 , which further comprises administering a therapeutically effective amount of an agent that inhibits HCMV-encoded DNA polymerase.991. The method of claim claim 82 , wherein the virus is HSV claim 82 , which further comprises administering a ...

Methods and Compositions Related to DLK-1 and the P38 MAPK Pathway in Nerve Regeneration

Disclosed are compositions and methods for treating neurodegenerative disease. 1C. elegans.. A method of regenerating axons , the method comprising activating a gene in the p38 MAPK pathway of2C. elegans.. A method of regenerating axons in a subject , the method comprising activating a gene with 80% or greater homology to a gene in the p38 MAPK pathway of3. The method of claim 2 , wherein the subject is a mammal.4. The method of claim 3 , wherein the mammal is a human.5. The method of or claim 3 , wherein the gene in the p38 MAPK pathway is selected from the group comprising dlk-1 claim 3 , mkk-4 claim 3 , and pmk-3.6C. elegans.. A method of regenerating axons claim 3 , the method comprising inhibiting a gene in the p38 MAPK pathway of7C. elegans.. A method of regenerating axons in a subject claim 3 , the method comprising inhibiting a gene with 80% or greater homology to a gene in the p38 MAPK pathway of8. The method of or claim 3 , wherein the subject is a mammal.9. The method of claim 8 , wherein the mammal is a human.10. The method of or claim 8 , wherein the gene in the p38 MAPK pathway is selected from the group comprising rpm-1 and fsn-1.11. The method of claim 7 , wherein the gene is inhibited with siRNA.12. The method of claim 11 , wherein the gene that is inhibited is phr-1.13C. elegans.. A method of treating a subject with a neurodegenerative disease claim 11 , the method comprising activating a gene with 80% or greater homology to a gene in the p38 MAPK pathway of14C. elegans.. A method of treating a subject with a neurodegenerative disease claim 11 , the method comprising inhibiting a gene with 80% or greater homology to a gene in the p38 MAPK pathway of15C. elegans. A method of regenerating axons in a subject claim 11 , the method comprising activating a gene with 80% or greater homology to a gene in the p38 MAPK pathway of by contacting the gene with a compound that activates said gene.16. A pharmaceutical composition comprising the compound of .17C. ...

Methods and compositions for improving sleep and memory

A method for determining whether a substance can increase the expression level of a fatty acid binding protein (FABP) in an animal. The method includes using a cell that includes an expression construct that comprises a FABP promoter operably linked to a polynucleotide sequence encoding a reporter molecule, wherein the cell is contacted with a candidate substance and then cultivating the cell under conditions conducive to expression of the reporter molecule. Increased expression of the construct in the presence of the candidate substance as compared to a control leads to improved sleep and long-term memory in the subject.

CNS TARGETING AAV VECTORS AND METHODS OF USE THEREOF

The invention in some aspects relates to recombinant adeno-associated viruses useful for targeting transgenes to CNS tissue, and compositions comprising the same, and methods of use thereof. In some aspects, the invention provides methods and compositions for treating CNS-related disorders. 1. A method for delivering a transgene to CNS tissue in a subject , the method comprising:administering an effective amount of a rAAV by intrathecal administration, wherein the rAAV comprises (i) a capsid protein comprising a sequence as set forth in SEQ ID NO: 9 and (ii) a nucleic acid comprising a promoter operably linked with a transgene.2. The method of further comprising administering an effective amount of the rAAV by intracerebral administration.3. A method for delivering a transgene to central nervous system (CNS) tissue in a subject claim 1 , the method comprising:administering an effective amount of a rAAV by intrathecal administration and by intracerebral administration, wherein the rAAV infects cells of CNS tissue in the subject and comprises a nucleic acid comprising a promoter operably linked with a transgene.4. The method of claim 2 , wherein the intracerebral administration is an intraventricular administration.5. The method of claim 1 , wherein the intrathecal administration is in the lumbar region of the subject6. The method of claim 4 , wherein the intraventricular administration is an administration into a ventricular region of the forebrain of the subject.7. The method of claim 1 , wherein the dose of the rAAV for intrathecal administration is in a range of 10genome copies to 10genome copies.8. The method of claim 2 , wherein the dose of the rAAV for intracerebral administration is in a range of 10genome copies to 10genome copies.9. The method of claim 1 , wherein the transgene is a CNS-associated gene.10. The method of claim 9 , wherein the CNS-associated gene is neuronal apoptosis inhibitory protein (NAIP) claim 9 , nerve growth factor (NGF) claim 9 , glial ...

METHODS OF ALTERING BONE GROWTH BY ADMINISTRATION OF SOST OR WISE ANTAGONIST OR AGONIST

The present invention provides a method of promoting local bone growth by administering a therapeutic amount of a Sost antagonist to a mammalian patient in need thereof. Preferably, the Sost antagonist is an antibody or FAB fragment selectively recognizing any one of SEQ ID NOS: 1-23. The Sost antagonist may be coadministered together or sequentially with a matrix conducive to anchoring new bone growth. Orthopedic and Periodontal devices comprising an implantable portion adapted to be permanently implanted within a mammalian body and bearing an external coating of a Sost antagonist are also disclosed, as it a method of increasing bone density by administering to a mammalian patient a therapeutic amount of a Sost antagonist together with an antiresorptive drug. 1. A method of increasing bone density in a mammalian patient in need thereof , comprising the steps of:systemically administering to a said mammalian patient a therapeutic comprising an effective amount of a Sclerostin antagonist sequentially with an antiresorptive drug.2. The method according to claim 1 , wherein said patient is a human.3. The method according to claim 2 , wherein said patient has low bone density.4. The method according to claim 3 , wherein said Sclerostin antagonist interferes with the interaction of Sclerostin with its receptor.5. The method according to claim 4 , wherein said Sclerostin antagonist is Usag-1 claim 4 , ectodin or sostdc1.6. The method according to claim 4 , wherein said Sclerostin antagonist is a Sclerostin mimetic or vinylogous peptoid.7. The method according to claim 3 , wherein said Sclerostin antagonist is siRNA or a nucleic acid aptamer.8. The method according to claim 7 , wherein said Sclerostin antagonist is Sc12.9. The method according to claim 3 , wherein said Sclerostin antagonist is an antibody or FAB fragment specifically binding a peptide selected from the group consisting of SEQ ID NOS:2-13 claim 3 , 22 and 23.10. The method according to claim 9 , wherein ...

Micro-RNA family that Modulates Fibrosis and Uses Thereof

The present invention relates to the identification of a microRNA family, designated miR-29a-c, that is a key regulator of fibrosis in cardiac tissue. The inventors show that members of the miR-29 family are down-regulated in the heart tissue in response to stress, and are up-regulated in heart tissue of mice that are resistant to both stress and fibrosis. Also provided are methods of modulating expression and activity of the miR-29 family of miRNAs as a treatment for fibrotic disease, including cardiac hypertrophy, skeletal muscle fibrosis other fibrosis related diseases and collagen loss-related disease. 188-. (canceled)89. A method of regulating expression of one or more extracellular matrix genes in a subject in need thereof comprising administering to the fibroblast cells of the subject a polynucleotide comprising a pri-miRNA , pre-miRNA , or mature sequence of miR-29a , miR-29b , and/or miR-29c , wherein the expression of one or more extracellular matrix genes in the fibroblast cells of the subject is reduced following administration of the polynucleotide.90. The method of claim 89 , wherein one or more extracellular matrix genes is elastin (ELN) claim 89 , fibrillin 1 (FBN1) claim 89 , collagen type I α1 (COL1A1) claim 89 , collagen type I α2 (COL1A2) claim 89 , collagen type III α1 (COL3A1) claim 89 , collagen type IV α4 (COL4A4) claim 89 , collagen type V α3 (COL5A3) claim 89 , collagen type XI α1 (COL11A1) claim 89 , collagen type V α1 (COL5A1) claim 89 , or collagen type IV α5 (COL4A5).91. The method of claim 89 , wherein the subject has tissue fibrosis or is identified as being at risk of developing tissue fibrosis.92. The method of claim 89 , wherein the tissue fibrosis is cardiac fibrosis claim 89 , scleroderma claim 89 , skeletal muscle fibrosis claim 89 , hepatic fibrosis claim 89 , kidney fibrosis claim 89 , pulmonary fibrosis claim 89 , or diabetic fibrosis.93. The method of claim 89 , wherein the polynucleotide comprises a sequence of SEQ ID NO: ...

DETECTION AND TREATMENT OF AUTOIMMUNE DISORDERS

Disclosed herein are methods of treatment of autoimmune diseases such as systemic lupus erythematosus (SLE) as well as clinical assays for detection of autoimmune disease activity in patients utilizing a PD1 ligand. 139.-. (canceled)40. A method of treating or preventing an autoimmune disease or treating or preventing the symptoms of an autoimmune disease comprising the steps of: identifying a patient in need of such treatment; and administering to the patient at least one caspase inhibitor in an amount sufficient to induce or increase PD-L1 expression by the cells of the patient , thereby treating or preventing the autoimmune disease or treating or preventing the symptoms of the autoimmune disease.41. The method of claim 40 , wherein the at least one caspase inhibitor comprises a poly-caspase inhibitor.42. The method of claim 40 , wherein the at least one caspase inhibitor comprises at least one of Z-WFHD-fmk claim 40 , Z-VDVAD-fmk claim 40 , Z-DEVD-fmk claim 40 , Z-YVAD-fmk claim 40 , Z-VE1D-fmk claim 40 , Z-IETD-fmk Z-LEHD-fmk claim 40 , Z-AEVD-fmk claim 40 , Z-LEED-fmk claim 40 , Z-VAD-fmk and OPH.43. The method of claim 40 , wherein the-caspase inhibitor is OPH.44. The method of claim 40 , wherein the autoimmune disease is SLE.45. The method of claim 40 , wherein the autoimmune disease is rheumatoid arthritis.46. The method of claim 40 , wherein the administering of the caspase inhibitor to the patient comprises at least one of intravenous claim 40 , intraperitoneal claim 40 , inhalation claim 40 , intramuscular claim 40 , subcutaneous claim 40 , nasal and oral administration.47. The method of claim 40 , further comprising the administration of at least one selected from therapeutics targeting HLA molecules claim 40 , CD18 claim 40 , CD2 claim 40 , CD4 claim 40 , CD28 claim 40 , Fc-gamma 3 receptor claim 40 , Fc gamma receptor 2a claim 40 , CTLA4 claim 40 , or TGF-b in an amount sufficient to induce or increase PD-L1 expression by the cells of the patient. This ...

COMPOSITIONS AND METHODS FOR THE TREATMENT OF A NEOPLASIA

The invention provides methods for the treatments of neoplasia featuring agents that interfere with the expression or activity of a TNFa receptor. 1. A method of reducing neoplastic cell survival or proliferation , the method comprising contacting a neoplastic cell with an agent that selectively reduces the expression or activity of a p75 or p55 TNF-α receptor in the neoplastic cell relative to an untreated control cell , thereby reducing neoplastic cell survival or proliferation.2. The method of claim 1 , wherein the method selectively reduces the expression or activity of the p75 TNF-α receptor in the neoplastic cell while the expression or activity of the p55 TNF-α receptor is not disrupted.3. The method of claim 1 , wherein the method selectively reduces the expression or activity of the p55 TNF-α receptor in the neoplastic cell while the expression or activity of the p75 TNF-α receptor is not disrupted.4. (canceled)5. The method of claim 1 , wherein the agent is an inhibitory nucleic acid molecule selected from the group consisting of an antisense molecule claim 1 , an siRNA claim 1 , and an shRNA that is complementary to at least a portion of a p75 or p55 TNF-α receptor nucleic acid molecule.6. (canceled)7. The method of claim 5 , wherein the inhibitory nucleic acid molecule comprises or consists essentially of a nucleic acid molecule with a sequence selected from the group consisting SEQ ID NO: 1 claim 5 , SEQ ID NO: 2 claim 5 , SEQ ID NO: 3 claim 5 , and SEQ ID NO: 4.8. The method of claim 1 , wherein the agent is an antibody or fragment thereof that selectively binds to the p75 or p55 TNF-α receptor.9. (canceled)10. The method of claim 1 , wherein the method increases cell death or reduces blood vessel formation in a neoplasia.11. A method of inhibiting angiogenesis or increasing cell death in a neoplasia claim 1 , the method comprising contacting a neoplastic or endothelial cell with an agent that selectively reduces the expression or activity of a p55 or ...

Modulation of nitric oxide signaling to normalize tumor vasculature

The instant invention provides methods for treating a solid tumor in a subject comprising modulating nitric oxide production in the tumor to normalize tumor vasculature and administering an anti-tumor therapy to the subject. The invention further provides methods of treating a solid tumor in a subject comprising selectively increasing cyclic guanosine monophosphate (cGMP) or cGMP dependent protein kinase G production in the tumor vasculature to an amount effective to normalize tumor vasculature and administering an anti-tumor therapy to the subject.