Inhibition of innate immune response

The present invention provides methods, kits, and compositions for reducing an innate immune system response in a human or animal cell, tissue or organism. One embodiment comprises: introducing an Agent mRNA comprising in vitro-synthesized mRNA encoding one or more proteins that affect the induction, activity or response of an innate immune response pathway; whereby, the innate immune response in the cell, tissue or organism is reduced compared to the innate immune response in the absence of the Agent mRNA. Other embodiments are methods, compositions and kits for using an Agent mRNA for treating a disease or medical condition in a human or animal that exhibits symptoms of an elevated innate immune system, or for reducing an innate immune response that is induced in a human or animal cell, tissue or organism by a Foreign Substance that is administered to the cell, tissue or organism.

COMPOSITIONS AND METHODS FOR REPROGRAMMING MAMMALIAN CELLS

The present invention relates to methods for changing the state of differentiation of a eukaryotic cell, the methods comprising introducing mRNA encoding one or more reprogramming factors into a cell and maintaining the cell under conditions wherein the cell is viable and the mRNA that is introduced into the cell is expressed in sufficient amount and for sufficient time to generate a cell that exhibits a changed state of differentiation compared to the cell into which the mRNA was introduced, and compositions therefor. For example, the present invention provides mRNA molecules and methods for their use to reprogram human somatic cells into pluripotent stem cells. 1. An ex vivo method for inducing a biological or biochemical effect in cells in culture that , comprising:repeatedly or continuously, at least once per day over a plurality of days, contacting the cells in culture with an RNA composition comprising in vitro-transcribed ssRNA or mRNA that encodes at least one protein, wherein the amount of dsRNA of a size greater than about 40 basepairs is less than about 0.001% of the total RNA in said RNA composition, and culturing the cells under conditions wherein said biological or biochemical effect is induced.2. The method of claim 1 , wherein said biological effect or biochemical effect is reprogramming the cells from a first differentiated state or phenotype to a second differentiated state of phenotype.3. The method of claim 1 , wherein the in vitro-transcribed ssRNA or mRNA encodes at least one protein selected from the group consisting of:i) OCT3/4, SOX1, SOX2, SOX3, SOX15, KLF1, KLF2, KLF4, KLF5, c-MYC, L-MYC, n-MYC, cMYC(T58A), LIN28, and NANOG; orii) MYOD or functional fragment or variant thereof, MYF5 or functional fragment or variant thereof, MYOGENIN or functional fragment or variant thereof, and MRF4 (MY6) or functional fragment or variant thereof; oriii) ASCL1 or functional fragment or variant thereof, MYT1L or functional fragment or variant thereof, ...

INHIBITION OF INNATE IMMUNE RESPONSE

The present invention provides methods, kits, and compositions for reducing an innate immune system response in a human or animal cell, tissue or organism. One embodiment comprises: introducing an Agent mRNA comprising in vitro-synthesized mRNA encoding one or more proteins that affect the induction, activity or response of an innate immune response pathway; whereby, the innate immune response in the cell, tissue or organism is reduced compared to the innate immune response in the absence of the Agent mRNA. Other embodiments are methods, compositions and kits for using an Agent mRNA for treating a disease or medical condition in a human or animal that exhibits symptoms of an elevated innate immune system, or for reducing an innate immune response that is induced in a human or animal cell, tissue or organism by a Foreign Substance that is administered to the cell, tissue or organism. 1. A method for reducing an innate immune response in a human or animal cell , tissue or organism , comprising:introducing into the cell, tissue or organism an Agent mRNA comprising in vitro-synthesized mRNA encoding one or more proteins that affect the induction, activity and/or response of an innate immune response pathway;whereby the innate immune response in the cell, tissue or organism is reduced compared to the innate immune response that results or would have resulted in the absence of introducing said Agent mRNA.2. The method of claim 1 , wherein said Agent mRNA encodes one or more proteins that inhibits the activity of an innate immune effector protein in a signaling pathway mediated by a TLR selected from the group consisting of TLR1 claim 1 , TLR2 claim 1 , TLR3 claim 1 , TLR4 claim 1 , TLR5 claim 1 , TLR6 claim 1 , TLR7 claim 1 , TLR8 claim 1 , TLR9 and TLR10 claim 1 , or a biologically active fragment claim 1 , analog or variant of any of said effector proteins.3. The method of claim 1 , wherein said Agent mRNA encodes one or more proteins that is a regulator or inhibitor of ...

INHIBITION OF INNATE IMMUNE RESPONSE

The present invention provides methods, kits, and compositions for reducing an innate immune system response in a human or animal cell, tissue or organism. One embodiment comprises: introducing an Agent mRNA comprising in vitro-synthesized mRNA encoding one or more proteins that affect the induction, activity or response of an innate immune response pathway; whereby, the innate immune response in the cell, tissue or organism is reduced compared to the innate immune response in the absence of the Agent mRNA. Other embodiments are methods, compositions and kits for using an Agent mRNA for treating a disease or medical condition in a human or animal that exhibits symptoms of an elevated innate immune system, or for reducing an innate immune response that is induced in a human or animal cell, tissue or organism by a Foreign Substance that is administered to the cell, tissue or organism. 1. A method for reducing an innate immune response in a human or animal cell , tissue or organism , comprising:introducing into the cell, tissue or organism an Agent mRNA comprising in vitro-synthesized mRNA encoding one or more proteins that affect the induction, activity and/or response of an innate immune response pathway;whereby the innate immune response in the cell, tissue or organism is reduced compared to the innate immune response that results or would have resulted in the absence of introducing said Agent mRNA.2. The method of claim 1 , wherein said Agent mRNA encodes one or more proteins that inhibits the activity of an innate immune effector protein in a signaling pathway mediated by a TLR selected from the group consisting of TLR1 claim 1 , TLR2 claim 1 , TLR3 claim 1 , TLR4 claim 1 , TLR5 claim 1 , TLR6 claim 1 , TLR7 claim 1 , TLR8 claim 1 , TLR9 and TLR10 claim 1 , or a biologically active fragment claim 1 , analog or variant of any of said effector proteins.3. The method of claim 1 , wherein said Agent mRNA encodes one or more proteins that is a regulator or inhibitor of ...

MAKING AND USING IN VITRO-SYNTHESIZED ssRNA FOR INTRODUCING INTO MAMMALIAN CELLS TO INDUCE A BIOLOGICAL OR BIOCHEMICAL EFFECT

The present invention relates to compositions, kits and methods for making and using RNA compositions comprising in vitro-synthesized ssRNA inducing a biological or biochemical effect in a mammalian cell or organism into which the RNA composition is repeatedly or continuously introduced. In certain embodiments, the invention provides compositions and methods for changing the state of differentiation or phenotype of a human or other vertebrate cell. For example, the present invention provides mRNA and methods for reprogramming cells that exhibit a first differentiated state or phenotype to cells that exhibit a second differentiated state or phenotype, such as to reprogram human somatic cells to pluripotent stem cells. 1. A composition or system comprising:a) single-stranded RNA (ssRNA) that encodes a protein, wherein the ssRNA is a product of in vitro transcription of a DNA template by an RNA polymerase;b) a double-stranded RNA (dsRNA) specific endoribonuclease III (endoRNase III) protein; andc) magnesium cations present at a concentration of about 1-4 mM.2. The composition or system of claim 1 , wherein said magnesium ions are present at a concentration of about 1-3 mM.3. The composition or system of claim 1 , wherein said ssRNA is characterized by at least one of the following:i) encodes a reprogramming factor;ii) encodes a CD protein, meaning a protein identified in the cluster of differentiation system;iii) encodes an enzyme;iv) encodes a protein in the immunoglobulin super family;v) encodes a cytokine or chemokine;vi) encodes a cell surface receptor protein;vi) encodes a protein in a cell signaling pathway;vii) encodes an antibody;viii) encodes a T cell receptor;vix) encodes a protein that reduces or suppresses an innate immune response comprising interferon (IFN) production or response;x) encodes a reporter protein;xi) contains one or more modified bases;xii) exhibits a cap structure;xiii) exhibits a Cap I structure where the 5′ penultimate nucleotide comprises ...

INHIBITION OF INNATE IMMUNE RESPONSE

The present invention provides methods, kits, and compositions for reducing an innate immune system response in a human or animal cell, tissue or organism. One embodiment comprises: introducing an Agent mRNA comprising in vitro-synthesized mRNA encoding one or more proteins that affect the induction, activity or response of an innate immune response pathway; whereby, the innate immune response in the cell, tissue or organism is reduced compared to the innate immune response in the absence of the Agent mRNA. Other embodiments are methods, compositions and kits for using an Agent mRNA for treating a disease or medical condition in a human or animal that exhibits symptoms of an elevated innate immune system, or for reducing an innate immune response that is induced in a human or animal cell, tissue or organism by a Foreign Substance that is administered to the cell, tissue or organism. 1. A method for reducing an innate immune response in a human or animal cell , tissue or organism , comprising:introducing into the cell, tissue or organism an Agent mRNA comprising in vitro-synthesized mRNA encoding one or more proteins that affect the induction, activity and/or response of an innate immune response pathway;whereby the innate immune response in the cell, tissue or organism is reduced compared to the innate immune response that results or would have resulted in the absence of introducing said Agent mRNA.2. The method of claim 1 , wherein said Agent mRNA encodes one or more proteins that inhibits the activity of an innate immune effector protein in a signaling pathway mediated by a TLR selected from the group consisting of TLR1 claim 1 , TLR2 claim 1 , TLR3 claim 1 , TLR4 claim 1 , TLR5 claim 1 , TLR6 claim 1 , TLR7 claim 1 , TLR8 claim 1 , TLR9 and TLR10 claim 1 , or a biologically active fragment claim 1 , analog or variant of any of said effector proteins.3. The method of claim 1 , wherein said Agent mRNA encodes one or more proteins that is a regulator or inhibitor of ...

MAKING AND USING IN VITRO-SYNTHESIZED ssRNA FOR INTRODUCING INTO MAMMALIAN CELLS TO INDUCE A BIOLOGICAL OR BIOCHEMICAL EFFECT

The present invention relates to compositions, kits and methods for making and using RNA compositions comprising in vitro-synthesized ssRNA inducing a biological or biochemical effect in a mammalian cell or organism into which the RNA composition is repeatedly or continuously introduced. In certain embodiments, the invention provides compositions and methods for changing the state of differentiation or phenotype of a human or other vertebrate cell. For example, the present invention provides mRNA and methods for reprogramming cells that exhibit a first differentiated state or phenotype to cells that exhibit a second differentiated state or phenotype, such as to reprogram human somatic cells to pluripotent stem cells. 1. A system comprising:a) single-stranded RNA (ssRNA) that encodes a protein, wherein the ssRNA is a product of in vitro transcription of a DNA template by an RNA polymerase;b) a double-stranded RNA (dsRNA) specific endoribonuclease III (endoRNase III) protein; andc) magnesium cations present at a concentration of about 1-4 mM.2. The system of claim 1 , wherein said magnesium ions are present at a concentration of about 1-3 mM.3. The system of claim 1 , wherein said ssRNA is characterized by at least one of the following:i) encodes a reprogramming factor;ii) encodes a CD protein, meaning a protein identified in the cluster of differentiation system;iii) encodes an enzyme;iv) encodes a protein in the immunoglobulin super family;v) encodes a cytokine or chemokine;vi) encodes a cell surface receptor protein;vi) encodes a protein in a cell signaling pathway;vii) encodes an antibody;viii) encodes a T cell receptor;vix) encodes a protein that reduces or suppresses an innate immune response comprising interferon (IFN) production or response;x) encodes a reporter protein;xi) contains one or more modified bases;xii) exhibits a cap structure;xiii) exhibits a Cap I structure where the 5′ penultimate nucleotide comprises a 2′-O-methyl-ribosyl group;xiv) exhibits a ...

MAKING AND USING IN VITRO-SYNTHESIZED ssRNA FOR INTRODUCING INTO MAMMALIAN CELLS TO INDUCE A BIOLOGICAL OR BIOCHEMICAL EFFECT

The present invention relates to compositions, kits and methods for making and using RNA compositions comprising in vitro-synthesized ssRNA inducing a biological or biochemical effect in a mammalian cell or organism into which the RNA composition is repeatedly or continuously introduced. In certain embodiments, the invention provides compositions and methods for changing the state of differentiation or phenotype of a human or other vertebrate cell. For example, the present invention provides mRNA and methods for reprogramming cells that exhibit a first differentiated state or phenotype to cells that exhibit a second differentiated state or phenotype, such as to reprogram human somatic cells to pluripotent stem cells.

Making and using in vitro-synthesized ssrna for introducing into mammalian cells to induce a biological or biochemical effect

The present invention relates to compositions, kits and methods for making and using RNA compositions comprising in vitro-synthesized ssRNA inducing a biological or biochemical effect in a mammalian cell or organism into which the RNA composition is repeatedly or continuously introduced. In certain embodiments, the invention provides compositions and methods for changing the state of differentiation or phenotype of a human or other vertebrate cell. For example, the present invention provides mRNA and methods for reprogramming cells that exhibit a first differentiated state or phenotype to cells that exhibit a second differentiated state or phenotype, such as to reprogram human somatic cells to pluripotent stem cells.

Making and using in vitro-synthesized ssrna for introducing into mammalian cells to induce a biological or biochemical effect

The present invention relates to compositions, kits and methods for making and using RNA compositions comprising in vitro-synthesized ssRNA inducing a biological or biochemical effect in a mammalian cell or organism into which the RNA composition is repeatedly or continuously introduced. In certain embodiments, the invention provides compositions and methods for changing the state of differentiation or phenotype of a human or other vertebrate cell. For example, the present invention provides mRNA and methods for reprogramming cells that exhibit a first differentiated state or phenotype to cells that exhibit a second differentiated state or phenotype, such as to reprogram human somatic cells to pluripotent stem cells.

Making and using in vitro-synthesized ssrna for introducing into mammalian cells to induce a biological or biochemical effect

The present invention relates to compositions, kits and methods for making and using RNA compositions comprising in vitro-synthesized ssRNA inducing a biological or biochemical effect in a mammalian cell or organism into which the RNA composition is repeatedly or continuously introduced. In certain embodiments, the invention provides compositions and methods for changing the state of differentiation or phenotype of a human or other vertebrate cell. For example, the present invention provides mRNA and methods for reprogramming cells that exhibit a first differentiated state or phenotype to cells that exhibit a second differentiated state or phenotype, such as to reprogram human somatic cells to pluripotent stem cells.

Preparation and use of in vitro synthesized ssRNA for introduction into mammalian cells to induce a biological or biochemical effect

Making and using in vitro-synthesized ssrna for introducing into mammalian cells to induce a biological or biochemical effect

Making and using in vitro-synthesized ssrna for introducing into mammalian cells to induce a biological or biochemical effect

The present invention relates to compositions, kits and methods for making and using RNA compositions comprising in vitro-synthesized ssRNA inducing a biological or biochemical effect in a mammalian cell or organism into which the RNA composition is repeatedly or continuously introduced. In certain embodiments, the invention provides compositions and methods for changing the state of differentiation or phenotype of a human or other vertebrate cell. For example, the present invention provides mRNA and methods for reprogramming cells that exhibit a first differentiated state or phenotype to cells that exhibit a second differentiated state or phenotype, such as to reprogram human somatic cells to pluripotent stem cells.

Making and using in vitro-synthesized ssrna for introducing into mammalian cells to induce a biological or biochemical effect

Making and using in vitro-synthesized ssrna for introducing into mammalian cells to induce a biological or biochemical effect

The present invention relates to compositions, kits and methods for making and using RNA compositions comprising in vitro-synthesized ssRNA inducing a biological or biochemical effect in a mammalian cell or organism into which the RNA composition is repeatedly or continuously introduced. In certain embodiments, the invention provides compositions and methods for changing the state of differentiation or phenotype of a human or other vertebrate cell. For example, the present invention provides mRNA and methods for reprogramming cells that exhibit a first differentiated state or phenotype to cells that exhibit a second differentiated state or phenotype, such as to reprogram human somatic cells to pluripotent stem cells.

Making and using in vitro-synthesized ssRNA for introducing into mammalian cells to induce a biological or biochemical effect

The present invention relates to compositions, kits and methods for making and using RNA compositions comprising in vitro-synthesized ssRNA inducing a biological or biochemical effect in a mammalian cell or organism into which the RNA composition is 5 repeatedly or continuously introduced. In certain embodiments, the invention provides compositions and methods for changing the state of differentiation or phenotype of a human or other vertebrate cell. For example, the present invention provides mRNA and methods for reprogramming cells that exhibit a first differentiated state or phenotype to cells that exhibit a second differentiated state or phenotype, such as to reprogram human somatic cells to 0 pluripotent stem cells. 267

Making and using in vitro-synthesized ssRNA for introducing into mammalian cells to induce a biological or biochemical effect

The present invention relates to compositions, kits and methods for making and using RNA compositions comprising in vitro-synthesized ssRNA inducing a biological or biochemical effect in a mammalian cell or organism into which the RNA composition is repeatedly or continuously introduced. In certain embodiments, the invention provides compositions and methods for changing the state of differentiation or phenotype of a human or other vertebrate cell. For example, the present invention provides mRNA and methods for reprogramming cells that exhibit a first differentiated state or phenotype to cells that exhibit a second differentiated state or phenotype, such as to reprogram human somatic cells to pluripotent stem cells.

Inhibition of innate immune response

The present invention provides methods, kits, and compositions for reducing an innate immune system response in a human or animal cell, tissue or organism. One embodiment comprises: introducing an Agent mRNA comprising in vitro-synthesized mRNA encoding one or more proteins that affect the induction, activity or response of an innate immune response pathway; whereby, the innate immune response in the cell, tissue or organism is reduced compared to the innate immune response in the absence of the Agent mRNA. Other embodiments are methods, compositions and kits for using an Agent mRNA for treating a disease or medical condition in a human or animal that exhibits symptoms of an elevated innate immune system, or for reducing an innate immune response that is induced in a human or animal cell, tissue or organism by a Foreign Substance that is administered to the cell, tissue or organism.