METHOD OF ENHANCING VIRAL-MEDIATED GENE DELIVERY
The invention provides methods for enhancing the delivery of viral vectors to the eye of a subject by administering a proteasome inhibitor or and a viral vector ending a gene of interest to the eye.
1 . A method of enhancing the delivery of a gene of interest to an eye of a subject comprising administering a proteasome inhibitor and a viral vector encoding the gene of interest to the eye.
2 . The method of claim 1 , wherein the proteasome inhibitor is doxorubicin (DOX), aclarubicin, bortezomib, lactacystin, disulfiram epigallocatechin-3-gallate marizomib (salinosporamide A), oprozomib (ONX-0912), delanzomib (CEP-18770) epoxomicin, MG132, beta-hydroxy beta-methylbutyrate or carfilzomib.
3 . The method of claim 1 , wherein the gene of interest is an opsin.
4 . The method of claim 3 , wherein the opsin is selected from the group consisting of channelrhodopsin, halorhodopsin, melanopsin, pineal opsin, bacteriorhodopsin, and proteorhodopsin, or a functional variant thereof.
5 . The method of claim 1 , wherein the gene of interest is operably linked to a cell-specific promoter.
6 . The method of claim 1 , wherein the viral vector is encapsulated in a nanoparticle, a polymer, or a liposome.
7 . The method of claim 1 , wherein the subject is suffering from an ocular disease or disorder.
8 . The method of claim 7 , wherein the ocular disease is retinoblastoma, ocular melanoma, diabetic retinopathy, hypertensive retinopathy, or an inflammation of ocular tissue.
9 . The method of claim 1 , wherein the proteasome inhibitor and the viral vector are delivered concurrently or sequentially.
10 . The method of claim 1 , wherein the viral vector is delivered to a retinal cell.
11 . The method of claim 10 , wherein the retinal cell is a retinal ganglion cell, a retinal bipolar cell, a retinal horizontal cell, an amacrine cell, a photoreceptor cell, a Müller glial cell, or a retinal pigment epithelial cell.
12 . The method of claim 1 or 9 , wherein the proteasome inhibitor and the viral vector are administered to the vitreous of the eye.
13 . The method of claim 1 or 9 , wherein the proteasome inhibitor and the viral vector are administered by a route wherein the administration is by injection or infusion.
14 . The method of claim 1 or 9 , wherein the proteasome inhibitor and the viral vector are not administered subretinally.
15 . A method of increasing light sensitivity or improving or restoring vision in a subject comprising administering a proteasome inhibitor and a viral vector that encodes an opsin to the vitreous of the eye.
16 . The method of claim 15 , wherein said opsin is selected from the group consisting of channelrhodopsin, halorhodopsin, melanopsin, pineal opsin, bacteriorhodopsin, and proteorhodopsin, or a functional variant thereof.
17 . The method of claim 15 , wherein the subject has an ocular disease or disorder.
18 . The method of any one of claims 15 - 17 , wherein the ocular disease is retinoblastoma, ocular melanoma, diabetic retinopathy, hypertensive retinopathy, or an inflammation of ocular tissues.