METHOD OF ENHANCING DELIVERY OF THERAPEUTIC COMPOUNDS TO THE EYE
The invention provides methods for enhancing the delivery of therapeutic compounds to the eye of a subject by administering plasmin or derivatives thereof and the therapeutic compounds to the eye.
1 . A method of enhancing the delivery of a therapeutic agent to an eye of a subject comprising administering a plasmin or derivative thereof and the therapeutic agent to the eye.
2 . The method of claim 1 , wherein the plasmin or derivative thereof is a miniplasmin or a microplasmin (ocriplasmin).
3 . The method of claim 1 , wherein the therapeutic agent is selected from a nucleic acid, a small molecule, an antibody, or a peptide.
4 . The method of claim 3 , wherein the nucleic acid is a nucleic acid expression vector, a plasmid, or an siRNA.
5 . The method of claim 4 , wherein nucleic acid expression vector is a viral vector comprising a transgene.
6 . The method of claim 5 , wherein the transgene is an opsin.
7 . The method of claim 6 , wherein the opsin is selected from the group consisting of channelrhodopsin, halorhodopsin, melanopsin, pineal opsin, bacteriorhodopisin, and proteorhodopsin, or a functional variant thereof.
8 . The method of claim 7 , wherein said transgene is operably linked to a cell-specific promoter.
9 . The method of claim 8 , wherein the therapeutic agent is encapsulated in a nanoparticle, a polymer, or a liposome.
10 . The method of claim 9 , wherein the therapeutic agent is selected from the group consisting of ranibizumab antibody FAB (Lucentis), VEGF Trap fusion molecule (VEGF Trap-Eye), macugen pegylated polypeptide (Pegaptanib), and bevacimzumab (Avastin).
11 . The method of claim 1 , wherein the subject is suffering from an ocular disease or disorder.
12 . The method of claim 1 , wherein the plasmin or derivative thereof and the therapeutic agent are delivered concurrently or sequentially.
13 . The method of claim 1 , wherein the therapeutic agent is delivered to a retinal cell.
14 . The method of claim 13 , wherein the retinal cell is a retinal ganglion cell, a retinal bipolar cell, a retinal horizontal cell, an amacrine cell, a photoreceptor cell, Müller glial cell, or a retinal pigment epithelial cell.
15 . The method of claim 1 , wherein the administration is to the vitreous of the eye.
16 . A method of increasing light sensitivity or improving or restoring vision in a subject comprising administering a plasmin or derivative thereof and a viral vector that encodes an opsin to the vitreous of the eye.
17 . The method of claim 16 , wherein said opsin is selected from the group consisting of channelrhodopsin, halorhodopsin, melanopsin, pineal opsin, bacteriorhodopisin, and proteorhodopsin, or a functional variant thereof.
18 . The method of claim 16 , wherein the subject has an ocular disease or disorder.