Compositions for treatment of wet age-related macular degeneration
A recombinant adeno-associated virus (rAAV) having an AAV8 capsid which is suitable for intra-retinal injection is provided herein. The rAAV comprises a vector genome packaged within the capsid which contains, operably linked to regulatory elements which direct expression of anti-human vascular endothelial growth factor (VEGF) antigen binding antibody fragment (aVEGF), a coding sequence for aVEGF, wherein the coding sequence is operably linked to regulatory elements which direct expression of the anti-VEGF Fab in the eye. Also provided herein are liquid suspensions containing these rAAV8.aVEGF and methods of using same for treatment of wet AMD and other ocular conditions.
1. A recombinant adeno-associated virus (rAAV) having an AAV8 capsid, wherein the rAAV comprises a vector genome packaged within the capsid, wherein the vector genome comprises a 5′ AAV-2 inverted terminal repeat, an expression cassette consisting of the contiguous nucleotides 198 to 3733 of SEQ ID NO: 14, and a 3′ AAV-2 inverted terminal repeat.
2. A liquid suspension suitable for sub-retinal and/or intra-retinal injection, said suspension comprising an aqueous liquid and the recombinant adeno-associated virus (rAAV) according to claim 1 and optionally one or more excipients, preservatives, and/or surfactants.
3. A product comprising: (a) a first container comprising the rAAV according to claim 1 and an aqueous liquid, (b) optionally a second container comprising a diluent, and (c) a needle for injection.
4. The suspension according to claim 2 , wherein the suspension comprises about 1×10 11 genome copies (GC)/mL to about 1×10 13 GC/mL of the rAAV.
5. The suspension according to claim 2 , wherein the suspension volume is about 10 μL to about 300 μL.