Systems and Methods for Nucleic Acid Expression In Vivo

The present invention provides compositions, systems, kits, and methods for generating expression of one or more proteins and/or biologically active nucleic acid molecules in a subject (e.g., at therapeutic levels for extended periods required to produce therapeutic effects). In certain embodiments, systems and kits are provided that comprise a first composition comprising a first amount of polycationic structures, and a second composition comprising a therapeutically effective amount of expression vectors (e.g., non-viral expression vectors not associated with liposomes) that are CpG-free or CpG-reduced, where the expression vectors comprise a first nucleic acid sequence encoding: i) a first therapeutic protein or proteins, and/or ii) a first biologically active nucleic acid molecule or molecules. 1. A method of expressing a first therapeutic protein and/or a biologically active nucleic acid molecule in a subject comprising:a) administering a first composition to a subject,wherein said subject has at least one symptom of a disease or condition, or has at least physiological trait to be altered,wherein said first composition comprises a first amount of polycationic structures, andwherein said first composition is free, or essentially free, of nucleic acid molecules; andb) administering a second composition to said subject within about 300 minutes of administering said first composition,wherein said second composition comprises a therapeutically effective amount of expression vectors,wherein said expression vectors are CpG-free or CpG-reduced,wherein said expression vectors each comprise a first nucleic acid sequence encoding: i) a first therapeutic protein, and/or ii) a first biologically active nucleic acid molecule,wherein the ratio of said first amount of said polycationic structures to said therapeutically effective amount of expression vectors is 5:1 to 25:1, andwherein, as a result of said administering said first composition and said administering said second ...

ENCAPSULATING LIPOSOMES

Provided herein is technology relating to liposomes and particularly, but not exclusively, to compositions of liposomes encapsulating a biologically active agent, methods of preparing liposomes encapsulating a biologically active agent, and uses of liposomes encapsulating a biologically active agent to treat a subject.

LIPOSOME LOADING

Provided herein is technology relating to incorporation of drugs into liposomes and particularly, but not exclusively, to methods for incorporating drugs into liposomes using a weak base and related compositions.

Liposome loading

Provided herein is technology relating to incorporation of drugs into liposomes and particularly, but not exclusively, to methods for incorporating drugs into liposomes using a weak base and related compositions.

ENCAPSULATING LIPOSOMES

Provided herein is technology relating to liposomes and particularly, but not exclusively, to compositions of liposomes encapsulating a biologically active agent, methods of preparing liposomes encapsulating a biologically active agent, and uses of liposomes encapsulating a biologically active agent to treat a subject. 1. A composition comprising liposomes , sulfate ions , and hydrogen ions , wherein the concentration of the hydrogen ions inside the liposomes is greater than the concentration of the hydrogen ions outside the liposomes.2. The composition of comprising sulfuric acid.3. The composition of claim 1 , wherein the interior of said liposomes has a pH of at least 3 pH units lower than the exterior of said liposomes.4. The composition of comprising a bioactive agent in the interior of the liposomes.5. The composition of wherein said bioactive agent is an analgesic.6. The composition of wherein said bioactive agent is an opioid.7. The composition of wherein said bioactive agent is selected from the group consisting of hydromorphone claim 4 , chloroquine claim 4 , and buprenorphine.8. The composition of wherein said bioactive agent is an antibiotic.9. The composition of claim 8 , wherein said antibiotic is doxycycline.10. The composition of wherein the bioactive agent is selected from the group consisting of an antitumor agent claim 4 , an anaesthetic claim 4 , an analgesic claim 4 , an antimicrobial agent claim 4 , a hormone claim 4 , an antiasthmatic agent claim 4 , a cardiac glycoside claim 4 , an antihypertensive claim 4 , a vaccine claim 4 , an antiarrhythmic claim 4 , an immunomodulator claim 4 , a steroid claim 4 , a monoclonal antibody claim 4 , a neurotransmitter claim 4 , a radionuclide claim 4 , a radio contrast agent claim 4 , a nucleic acid claim 4 , a protein claim 4 , a herbicide claim 4 , a pesticide claim 4 , and suitable combinations thereof.11. The composition of comprising an aqueous buffer and a base outside the liposomes.12. The ...

Systems and Methods for Nucleic Acid Expression In Vivo

The present invention provides compositions, systems, kits, and methods for generating expression of one or more proteins and/or biologically active nucleic acid molecules in a subject (e.g., at therapeutic levels for extended periods required to produce therapeutic effects). In certain embodiments, systems and kits are provided that comprise a first composition comprising a first amount of polycationic structures, and a second composition comprising a therapeutically effective amount of expression vectors (e.g., non-viral expression vectors not associated with liposomes) that are CpG-free or CpG-reduced, where the expression vectors comprise a first nucleic acid sequence encoding: i) a first therapeutic protein or proteins, and/or ii) a first biologically active nucleic acid molecule or molecules. 1. A method of expressing an antibody light chain and/or heavy chain in a subject comprising:a) administering intravenously a first composition to a subject,wherein said first composition comprises a first amount of polycationic structures, andwherein said first composition is free, or essentially free, of nucleic acid molecules; andb) administering intravenously a second composition to said subject within about 300 minutes of administering said first composition,wherein said second composition comprises non-viral expression vectors,wherein said non-viral expression vectors are CpG-free or CpG-reduced,wherein said non-viral expression vectors each comprise the same first nucleic acid sequence encoding an antibody light chain and/or heavy chain,wherein the ratio of said first amount of said polycationic structures to said non-viral expression vectors is 5:1 to 25:1, andwherein, as a result of said administering said first composition and said administering said second composition, said antibody light chain and/or heavy chain is expressed in said subject at a level of at least 50 pg/ml in serum for at least 7 consecutive days; andc) administering intravenously a drug agent, ...

Systems and Methods for Nucleic Acid Expression In Vivo

The present invention provides compositions, systems, kits, and methods for generating expression of one or more proteins and/or biologically active nucleic acid molecules in a subject (e.g., at therapeutic levels for extended periods required to produce therapeutic effects). In certain embodiments, systems and kits are provided that comprise a first composition comprising a first amount of polycationic structures, and a second composition comprising a therapeutically effective amount of expression vectors (e.g., non-viral expression vectors not associated with liposomes) that are CpG-free or CpG-reduced, where the expression vectors comprise a first nucleic acid sequence encoding: i) a first therapeutic protein or proteins, and/or ii) a first biologically active nucleic acid molecule or molecules.

LIPOSOME LOADING

Provided herein is technology relating to incorporation of drugs into liposomes and particularly, but not exclusively, to methods for incorporating drugs into liposomes using a weak base and related compositions. 1. A liposome composition for preparing liposomes loaded with a bioactive agent , the composition comprising liposomes , the liposomes comprising a loading base in the intraliposomal space , the loading base having a pKa that is less than a pKa of the bioactive agent.2. The liposome composition of further comprising a loading medium in the extraliposomal space claim 1 , the loading medium having a pH that is greater than the pKa of the loading base.3. The liposome composition of wherein the loading medium comprises a buffer.4. The liposome composition of wherein the concentration of the loading base in the intraliposomal space is greater than the concentration of the loading base in the extraliposomal space.5. The liposome composition of wherein the (log P−pKa) of the loading base is greater than the (log P−pKa) of the bioactive agent.6. The liposome composition of wherein the loading base is a pyridine or pyridine derivative.7. The composition of wherein the loading base is a pyridinium claim 1 , a 2-methoxy-pyridinium claim 1 , or a pyridazinium.8. The composition of wherein the loading base is adenine or an adenine derivative.9. The composition of wherein the loading base is aniline or an aniline derivative.10. The composition of wherein the loading base is nicotinamide or a nicotinamide derivative.11. The composition according to wherein the pKa of the loading base is less than 6 claim 1 , less than 5 claim 1 , less than 4 claim 1 , less than 3 claim 1 , or less than 2.12. The composition according to wherein the log P of the loading base is less than 1.5 claim 1 , less than 1.0 claim 1 , less than 0.5 claim 1 , less than 0.0 claim 1 , or less than −0.5.13. The composition of wherein the liposomes comprise phosphatidylcholine.14. The composition of ...

SYSTEMS AND METHODS FOR NUCLEIC ACID EXPRESSION IN VIVO

The present invention provides compositions, systems, kits, and methods for expression of one or more biomolecules in a subject, human or non-human mammal, (e.g., at therapeutic levels for the extended periods of time required to produce therapeutic effects). In certain embodiments, compositions, systems, kits, and methods are provided that comprise a first composition comprising polycationic structures (e.g., empty cationic liposomes, cationic micelles, cationic emulsions, or cationic polymers) and a second composition comprising expression vectors (e.g., non-viral expression vectors not associated with liposomes or other carriers) encoding one or more biomolecules of interest. 1. A system comprising:a) a first composition comprising a first amount of polycationic structures, wherein said first composition is free, or essentially free, of nucleic acid molecules; andb) a second composition comprising a therapeutically effective amount of expression vectors,wherein said expression vectors comprise nucleic acid sequences encoding one or more therapeutic biomolecules; andat least one of the following:i) wherein the ratio of said first amount of said polycationic structures to said therapeutically effective amount of expression vectors is 5:1 to 25:1;ii) wherein 2.0% to 15.0% of said first composition comprises dexamethasone palmitate and/or dexamethasone;iii) wherein said first composition further comprises neutral lipid; andiv) wherein said polycationic structures comprise empty liposomes, and wherein said empty liposomes present in said first composition have a z-average diameter of about 20-85 nm.2. The system of claim 1 , wherein said expression vectors comprise circularized synthetically amplified nucleic acid claim 1 , plasmid-based vector claim 1 , or minicircle DNA.3. The system of claim 1 , wherein said one or more therapeutic biomolecules comprise one or more monoclonal antibodies (mAb) claim 1 , or antigen-binding portion thereof.4. The system of claim 3 , ...

Catonic amphiphiles

Cationic amphiphiles are provided that are alkyl or alkoxyalkyl O-phosphate esters of diacylphosphatidyl zwitterionic compounds such as phosphatidylcholine or phosphatidyl ethanolamine. The amphiphiles can be used as carriers for delivering macromolecules intracellularly.

Systems and methods for nucleic acid expression in vivo

The present invention provides compositions, systems, kits, and methods for generating expression of one or more proteins and/or biologically active nucleic acid molecules in a subject (e.g., at therapeutic levels for extended periods required to produce therapeutic effects). In certain embodiments, systems and kits are provided that comprise a first composition comprising a first amount of polycationic structures, and a second composition comprising a therapeutically effective amount of expression vectors (e.g., non-viral expression vectors not associated with liposomes) that are CpG-free or CpG-reduced, where the expression vectors comprise a first nucleic acid sequence encoding: i) a first therapeutic protein or proteins, and/or ii) a first biologically active nucleic acid molecule or molecules.

Cationic amphiphiles

Cationic amphiphiles are provided that are alkyl or alkoxyalkyl O-phosphate esters of diacylphosphatidyl zwitterionic compounds such as phosphatidylcholine or phosphatidyl ethanolamine. The amphiphiles can be used as carriers for delivering macromolecules intracellularly.

Liposome conjugates and diagnostic methods therewith

A number of naturally occurring antibodies to human erythrocyte surface antigens are capable of combining with their specific antigens (for example, Rhesus factor), but are not capable of producing visible hemagglutination. Also, the sensitivity of many diagnostic methods, such as in human blood typing, depends upon cell agglutination. The present invention provides liposome-protein conjugates, especially useful for hemagglutination assays, having an enhanced agglutination capacity with respect to antibody from The invention described herein was made in the course of work under a grant or award from the Department of Health and Human Services.

Cationic amphiphiles

Cationic amphiphiles are provided that are alkyl or alkoxyalkyl O-phosphate esters of diacylphosphatidyl zwitterionic compounds such as phosphatidylcholine or phosphatidyl ethanolamine. The amphiphiles can be used as carriers for delivering macromolecules intracellularly.

Covalently bonded liposome-protein-compositions and method of producing them

Activated liposome having various material encapsulated by outer surfaces thereof are disclosed. The outer surfaces include lipid molecules, at least some of which have been modified by an oxidation reaction and which function as covalent binding sites for a variety of proteins, most particularly for IgG. When biologically active proteins are covalently bound, or coupled, to the activated liposomes, the encapsulated materials remain captured within the activated liposomes, and the coupled proteins retain a significant amount of biological activity.

Liposome-encapsulated opioid analgesics

Liposome-encapsulated opioid formulations and methods of use for long-term analgesic activity in animals are provided.

Amphiphilic derivatives of piperazine

Novel, heterocyclic cationic amphiphile and compounds thereof are prepared that are degraded in vivo. Liposomes are produced from the cations that are used as carriers for delivering macromolecules intracellularly and may be targeted to a specific cell type.

Systems and methods for nucleic acid expression in vivo

Amphiphilic biguanide derivatives

Cationic derivatives of biguanide are provided, which are useful in the preparation of lipid carriers for mediating transfection of mammalian cells in vivo and in vitro.

Cationic amphiphiles

Kationiske amfifiler som er alkyl eller alkoksyalkyl O-fosfatestere av diacylfosfatidyl zwitterioniske forbindelser så som fosfatidylcholin eller fosfatidyletanolamin er beskrevet. Amfifiler kan bli anvendt som bærere for levering av makromolekyler intracellulært.

Amphiphilic derivatives of guanidine

Guanidin-baserte amfifiler som er ikke-toksiske overfor vertspattedyret, spesielt en human vert er beskrevet. Amfifilene blir anvendt for å produsere liposomer nyttige som bærere for levering av makromolekyler intracellulaert.

Systems and methods for nucleic acid expression in vivo

The present invention provides compositions, systems, kits, and methods for expression of one or more biomolecules in a subject, human or non-human mammal, (e.g., at therapeutic levels for the extended periods of time required to produce therapeutic effects). In certain embodiments, compositions, systems, kits, and methods are provided that comprise a first composition comprising polycationic structures (e.g., empty cationic liposomes, cationic micelles, cationic emulsions, or cationic polymers) and a second composition comprising expression vectors (e.g., non-viral expression vectors not associated with liposomes or other carriers) encoding one or more biomolecules of interest.

Amphiphilic derivatives of piperazine

Novel, heterocyclic cationic amphiphile and compounds thereof are prepared that are degraded in vivo. Liposomes are produced from the cations that are used as carriers for delivering macromolecules intracellularly and may be targeted to a specific cell type.

Liposome conjugates and diagnostic methods therewith

Liposome Conjugates and Diagnostic Methods Therewith Abstract A number of naturally occurring antibodies to human erythrocyte surface antigens are capable of combin-ing with their specific antigens (for example, Rhesus factor), but are not capable of producing visible hemagglutination. Also, the sensitivity of many diag-nostic methods, such as in human blood typing, depends upon cell agglutination. The present invention provides liposome-protein conjugates, especially useful for he-magglutination assays, having an enhanced agglutination capacity with respect to antibody from which the conju-gates are derived.

Metodo per determinare la presenza di analita in soluzione, in particolare per saggi immunologici

Systems and methods for nucleic acid expression in vivo

The present invention provides compositions, systems, kits, and methods for expression of one or more biomolecules in a subject, human or non-human mammal, (e.g., at therapeutic levels for the extended periods of time required to produce therapeutic effects). In certain embodiments, compositions, systems, kits, and methods are provided that comprise a first composition comprising polycationic structures (e.g., empty cationic liposomes, cationic micelles, cationic emulsions, or cationic polymers) and a second composition comprising expression vectors (e.g., non-viral expression vectors not associated with liposomes or other carriers) encoding one or more biomolecules of interest.

Amfifiliske imidazoliniumderivater

Amfifiliske derivater av piperazin

Nye, heterocykliske kationiske amfifile forbindelser blir fremstilt og som blir degradert in vivo. Liposomer blir produsert fra kationer som blir anvendt som bærere for levering av makromolekyler intracellulært og kan bli målsøkt til en spesifikk celletype.

Nitrogen containing amphiphiles and their use in liposomes for delivering genetic material intracellularly

Amphiphiles containing an imidazdinium ring system are provided that are non-toxic to the host mammal. The amphiphiles are used to produce liposomes useful as carriers for delivering macromolecules intracellularly.

Amphiphilic imidazolinium derivatives

Amphiphiles containing an imidazdinium ring system are provided that are non-toxic to the host mammal. The amphiphiles are used to produce liposomes useful as carriers for delivering macromolecules intracellularly.

Amphiphile imidazolinium-derivate

Kovalent gebundene liposom-protein-verbindungen und verfahren zu deren herstellung.

Amfifiliske imidazoliniumderivater

Systems and methods for nucleic acid expression in vivo

The present invention provides compositions, systems, kits, and methods for generating expression of one or more proteins and/or biologically active nucleic acid molecules in a subject (e.g., at therapeutic levels for extended periods required to produce therapeutic effects). In certain embodiments, systems and kits are provided that comprise a first composition comprising a first amount of polycationic structures, and a second composition comprising a therapeutically effective amount of expression vectors (e.g., non-viral expression vectors not associated with liposomes) that are CpG-free or CpG-reduced, where the expression vectors comprise a first nucleic acid sequence encoding: i) a first therapeutic protein or proteins, and/or ii) a first biologically active nucleic acid molecule or molecules.

インビボでの核酸発現のためのシステム及び方法

【課題】対象において１つ以上のタンパク質及び／または生物学的に活性な核酸分子を発現させるための組成物、システム、キット及び方法を提供する。【解決手段】方法は、ａ）第１の組成物を対象に投与し、前記対象は、疾患または病態の少なくとも１つの症状を有するか、または少なくとも変化する生理学的形質を有し、前記第１の組成物は第１の量のポリカチオン性構造体を含み、前記第１の組成物は核酸分子を含んでいないか、実質的に含んでおらず、ｂ）前記第１の組成物を投与して約３００分以内に前記対象に第２の組成物を投与し、前記第２の組成物は、治療有効量の発現ベクターを含み、前記発現ベクターはＣｐＧ非含有またはＣｐＧが減少されており、前記発現ベクターは、それぞれ、ｉ）第１の治療用タンパク質及び／またはｉｉ）第１の生物学的に活性な核酸分子をコードする第１の核酸配列を含む。【選択図】図１

Liposome loading

Provided herein is technology relating to incorporation of drugs into liposomes and particularly, but not exclusively, to methods for incorporating drugs into liposomes using a weak base and related compositions.