IP Library › Granted Patent US 12,649,004
Granted Patent B2
US 12,649,004 · App. 17/425,292 · Granted Jun 9, 2026

Highly efficient transduction and lateral spread in the retina by a novel AAV virus enhanced by rational design

Inventors: Shannon E. Boye (Gainesville, FL); Sanford L. Boye (Gainesville, FL)
Assignee: University of Florida Research Foundation, Incorporated
A61K48/0058A61K48/0075C07K14/005C12N15/86C12N2750/14122C12N2750/14143
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Quick Facts
Patent No.
US 12,649,004
App. No.
17/425,292
Granted
Jun 9, 2026
Kind
B2
Abstract

rAAV particles comprising a new capsid variant, AAV44.9(E531D) are described herein, as well as a polynucleotide encoding same, and the use of the rAAV particles in the treatment of the eye, including treatment of retinal disorders. The disclosure also shows that the rAAV particles comprising an AAV44.9(E531D) capsid exhibit enhanced lateral spread after subretinal injection to a fovea of the subject, wherein detachment of the fovea is minimized. Methods of treatment comprising administering rAAV particles to a mammal in need thereof, and methods of transducing photoreceptor and RPE cells with rAAV particles, are also provided.

Claims (19)

1 . A recombinant adeno-associated viral (rAAV) particle comprising a capsid protein comprising the amino acid sequence of SEQ ID NO: 3.

2 . The rAAV particle of claim 1 , further comprising a VP1 capsid protein and a VP2 capsid protein, wherein the VP1 capsid protein comprises the amino acid sequence of SEQ ID NO: 1 and the VP2 capsid protein comprises the amino acid sequence of SEQ ID NO: 2.

3 . The rAAV particle of claim 1 , further comprising a heterologous nucleic acid sequence operably linked to one or more regulatory sequences that direct expression of the heterologous nucleic acid sequence in a photoreceptor (PR) cell or a retinal pigment epithelium (RPE) cell, wherein the heterologous nucleic acid sequence comprises GUCY2D, AIPL1, LCA5, RPGRIP1, CRX, CRB1, NMNAT1, CEP290, IMPDH1, RD3, RDH12, TULP1, KCNJ13, GDF6, IQCB1, SPATA7 or PRPH2.

4 . The rAAV particle of claim 3 , wherein the one or more regulatory sequences comprises a human rhodopsin kinase (hGRK1) promoter.

5 . The rAAV particle of claim 3 , wherein the heterologous nucleic acid sequence encodes a peptide.

6 . A composition comprising the rAAV particle of claim 1 , further comprising one or more pharmaceutically acceptable carriers, buffers, diluents or excipients.

7 . The rAAV particle of claim 6 , wherein the one or more pharmaceutically acceptable carriers, buffers, diluents or excipients comprises balanced salt solution.

8 . The rAAV particle of claim 6 , wherein the one or more pharmaceutically acceptable carriers, buffers, diluents or excipients comprises polysorbate 20.

9 . The rAAV particle of claim 6 , wherein the one or more pharmaceutically acceptable carriers, buffers, diluents or excipients comprises balanced salt solution supplemented with 0.014% w/v polysorbate 20.

10 . An isolated cell comprising the rAAV particle of claim 1 .

11 . The rAAV particle of claim 1 , further comprising a heterologous nucleic acid sequence comprising a sequence selected from ABCA4, CRX, GUCA1A (GCAP1) and GUCA1B (GCAP2).

12 . The rAAV particle of claim 1 , further comprising a heterologous nucleic acid sequence, wherein the heterologous nucleic acid sequence comprises RS1.

13 . The rAAV particle of claim 1 , further comprising a heterologous nucleic acid sequence comprising a sequence selected from BBS1, BBS2, ARL6/BBS3, BBS4, BBS5, BBS7, TTC8/BBS8, BBS10, TRIM32/BBS11, BBS12, CCDCC28B, CEP290, TMEM67, MKS1 and MKKS.

14 . The rAAV particle of claim 1 , further comprising a heterologous nucleic acid sequence comprising a sequence selected from RHO, PRPF31, RP1, NRL, NR2E3, RPGR, RP2, PDE6A, PDE6B, PDE6G, RP25, CNGA1, CNGB1 and MAK.

15 . The rAAV particle of claim 1 , further comprising a heterologous nucleic acid sequence comprising a sequence selected from OPN1LW, OPN1MW, CNGB3, CNGA3, and GNAT2.

16 . The rAAV particle of claim 1 , further comprising a heterologous nucleic acid sequence comprising a sequence selected from MYO7A, USH1C, CDH23, PCDH15 and USH1G, USH2A, DFNB31, and CLRN1.

17 . The rAAV particle of claim 1 , further comprising a heterologous nucleic acid sequence comprising a sequence selected from GUCY2D, AIPL1, LCA5, RPGRIP1, CRX, CRB1, NMNAT1, CEP290, IMPDH1, RD3, RDH12, TULP1, KCNJ13, GDF6, IQCB1, SPATA7 and PRPH2.

18 . A capsid protein comprising the amino acid sequence of any one of SEQ ID NOs: 1, 2, and 3.

19 . A nucleic acid molecule comprising the nucleic acid sequence of any one of SEQ ID NOs: 4, 5, and 6.

Assignments (2)
CONFIRMATORY LICENSE Recorded Dec 6, 2023
From: UNIVERSITY OF FLORIDA
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 065791/0644 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 31, 2021
From: BOYE, SANFORD L.; BOYE, SHANNON E.
To: UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INCORPORATED
Reel/Frame 057978/0543 →
Continuity (2)
Provisional Application 62795695 · Jan 23, 2019
Related Publication 20220133909A1 · May 5, 2022
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