Adeno-associated viral vectors for treating myocilin (myoc) glaucoma
AssigneeGenzyme Corporation
InventorsPeter PECHAN, Abraham SCARIA, Jeffery ARDINGER
Life of this patent
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Abstract
Provided herein are methods for treating myocilin (MYOC) glaucoma using adeno-associated viral (AAV) vectors. In some aspects, the AAV vectors encode R-spondin 1 (RSPO1), R-spondin 2 (RSPO2), R-spondin 3 (RSPO3) or R-spondin 4 (RSPO4) and/or RNAi that targets myocilin (MYOC). In one aspect, viral particles are administered to the eye of a human subject. Viral particles encoding RSPO1, RSPO2, RSPO3 and/or RSPO4 and/or MYOC RNAi are contemplated. In some aspects, variant AAV2 particles that transduce the trabecular meshwork are provided.
Claims281
A method for treating myocilin (MYOC) glaucoma in a mammal, comprising administering to the eye of the mammal an agent that increases Wnt signaling in the eye of the mammal.
A method for treating myocilin (MYOC) glaucoma in a mammal, comprising administering to the eye of the mammal a recombinant adeno-associated virus (rAAV) particle comprising a vector encoding RSPO1, RSPO2, RSPO3, RSPO4, or a functional variant thereof.
A method for treating myocilin (MYOC) glaucoma in a mammal, comprising administering to the eye of the mammal an agent that reduces or inhibits expression of a myocilin (MYOC) in the mammal.
A method for treating myocilin (MYOC) glaucoma in a mammal, comprising administering to the eye of the mammal a recombinant adeno-associated virus (rAAV) particle comprising a vector encoding a MYOC RNAi which targets expression of a myocilin (MYOC) in the mammal.
A method for treating myocilin (MYOC) glaucoma in a mammal, comprising administering to the eye of the mammal an agent that increases Wnt signaling in the eye of the mammal and an agent that reduces or inhibits expression of myocilin in the mammal.
A method for treating myocilin (MYOC) glaucoma in a mammal, comprising administering to the eye of the mammal a recombinant adeno-associated virus (rAAV) particle comprising a vector encoding RSPO1, RSPO2, RSPO3, RSPO4, or a functional variant thereof, and a rAAV particle comprising a vector encoding a MYOC RNAi which targets expression of a myocilin in the mammal.
A method for treating myocilin (MYOC) glaucoma in a mammal, comprising administering to the eye of the mammal a recombinant adeno-associated virus (rAAV) particle comprising a vector encoding RSPO1, RSPO2, RSPO3, RSPO4, or a functional variant thereof, and encoding a MYOC shRNA which targets expression of a myocilin (MYOC shRNA) in the mammal.
A method for enhancing Wnt signaling in trabecular meshwork cells in a mammal having an ocular disorder, comprising administering to the eye of the mammal a recombinant adeno-associated virus (rAAV) particle comprising a vector encoding RSPO1, RSPO2, RSPO3, RSPO4, or a functional variant thereof.
A method for enhancing Wnt signaling in trabecular meshwork cells in a mammal having an ocular disorder, comprising administering to the eye of the mammal a recombinant adeno-associated virus (rAAV) particle comprising a vector encoding a MYOC RNAi which targets expression of a myocilin (MYOC) in the mammal.
A method for enhancing Wnt signaling in trabecular meshwork cells in a mammal having an ocular disorder, comprising administering to the eye of the mammal a recombinant adeno-associated virus (rAAV) particle comprising a vector encoding RSPO1, RSPO2, RSPO3, RSPO4, or a functional variant thereof, and a rAAV particle comprising a vector encoding a MYOC RNAi which targets expression of a myocilin in the mammal.
A method for enhancing Wnt signaling in trabecular meshwork cells in a mammal having an ocular disorder, comprising administering to the eye of the mammal a recombinant adeno-associated virus (rAAV) particle comprising a vector encoding RSPO1, RSPO2, RSPO3, RSPO4, or a functional variant thereof, and encoding a MYOC RNAi which targets expression of a myocilin in the mammal.
A recombinant AAV particle comprising an AAV vector, wherein the AAV vector comprises nucleic acid encoding RSPO1, RSPO2, RSPO3, RSPO4, or a functional variant thereof.
A recombinant AAV particle comprising an AAV vector, wherein the AAV vector comprises nucleic acid encoding an inhibitory nucleic acid that targets expression of a myocilin (MYOC) in the mammal.
A recombinant AAV particle comprising an AAV vector, wherein the AAV vector comprises nucleic acid encoding RSPO1, RSPO2, RSPO3, RSPO4, or a functional variant thereof, and encoding an inhibitory nucleic acid that targets expression of a myocilin (MYOC) in the mammal.
A kit for treating myocilin (MYOC) glaucoma in a mammal comprising a rAAV viral particle comprising a vector encoding RSPO1, RSPO2, RSPO3, RSPO4, or a functional variant thereof.
A kit for treating myocilin (MYOC) glaucoma in a mammal comprising a rAAV viral particle comprising an AAV vector, wherein the AAV vector comprises nucleic acid encoding an inhibitory nucleic acid which targets expression of a myocilin (MYOC) in the mammal.
A kit for treating myocilin (MYOC) glaucoma in a mammal comprising a rAAV viral particle comprising an AAV vector, wherein the AAV vector comprises nucleic acid encoding RSPO1, RSPO2, RSPO3, RSPO4, or a functional variant thereof, and encoding an inhibitory nucleic acid which targets expression of a myocilin (MYOC) in the mammal.
A method of delivering nucleic acid to the trabecular meshwork of the eye of a mammal, comprising administering an AAV serotype 2 (AAV2) particle comprising a rAAV vector to the eye of the mammal, wherein the rAAV vector comprises the nucleic acid, and wherein the AAV2 particle comprises AAV2 capsid protein comprising a R471A amino acid substitution, numbering based on VP1 of AAV2.
A method of treating an ocular disorder in a mammal comprising administering a AAV2 particle comprising a rAAV vector to the eye of the mammal, wherein the rAAV vector comprises nucleic acid encoding a therapeutic transgene, and wherein the AAV2 particle comprises AAV2 capsid protein comprising a R471A amino acid substitution, numbering based on VP1 of AAV2.
A recombinant AAV2 particle for delivering nucleic acid to the trabecular meshwork of the eye of a mammal, wherein the AAV2 particle comprises a rAAV vector, wherein the rAAV vector comprises the nucleic acid, and wherein the AAV2 particle comprises AAV2 capsid protein comprising a R471A amino acid substitution, numbering based on VP1 of AAV2.
A recombinant AAV2 particle for treating an ocular disorder in a mammal wherein the AAV2 particle comprises a rAAV vector, wherein the rAAV vector comprises nucleic acid encoding a therapeutic transgene, and wherein the AAV2 particle comprises AAV2 capsid protein comprising a R471A amino acid substitution, numbering based on VP1 of AAV2.
Use of a recombinant AAV2 particle for delivering nucleic acid to the trabecular meshwork of the eye of a mammal, wherein the AAV2 particle comprises a rAAV vector, wherein the rAAV vector comprises the nucleic acid, and wherein the AAV2 particle comprises AAV2 capsid protein comprising a R471A amino acid substitution, numbering based on VP1 of AAV2.
Use of a recombinant AAV2 particle for treating an ocular disorder in a mammal wherein the AAV2 particle comprises a rAAV vector, wherein the rAAV vector comprises nucleic acid encoding a therapeutic transgene, and wherein the AAV2 particle comprises AAV2 capsid protein comprising a R471A amino acid substitution, numbering based on VP1 of AAV2.
A kit delivering nucleic acid to the trabecular meshwork of the eye of a mammal, comprising a rAAV2 particle comprising a rAAV vector, wherein the rAAV vector comprises the nucleic acid, and wherein the AAV2 particle comprises AAV2 capsid protein comprising a R471A amino acid substitution, numbering based on VP1 of AAV2.
A kit for treating an ocular disorder in a mammal comprising a rAAV2 particle comprising a rAAV vector, wherein the rAAV vector comprises nucleic acid encoding a therapeutic transgene, and wherein the AAV2 particle comprises AAV2 capsid protein comprising a R471A amino acid substitution, numbering based on VP1 of AAV2.
Dependencies are inferred from the claim text.