Modified aav capsid proteins and uses thereof
AssigneesUniversity of Florida Research Foundation, Inc., The UAB Research Foundation
InventorsSergei Zolotukhin, Sanford L. Boye, Shannon E. Boye, Damien Marsic, Nicholas Muzyczka, Hector Ruben Mendez-Gomez, Paul D. Gamlin
Life of this patent
Estimating the term…
Abstract
Adeno associated viral (AAV) particles are emerging as useful vehicle for gene delivery to various organs and tissues, one of them being the retina. Provided here are variant AAV (e.g., variant serotype 2 (AAV2)) capsid proteins and variant capsid protein containing particles with enhanced ability to transduce retinal cells.
Claims7
A variant recombinant adeno-associated virus (rAAV) serotype 2 (AAV2) capsid protein comprising sequences DGE and DF in variable region (VR) V (VRV) and any one of the following sets of sequences and/or substitutions:
- (a) EDATENXIXXDR (SEQ ID NO:
- 4) in VRVII,
- (b) NA in VRI;
- and SAAGADXAXDS (SEQ ID NO:
- 5) in VRVII,
- (c) NA in VRI;
- and EDATENXIXXDR (SEQ ID NO:
- 4) in VRVII,
- (d) SAAGADXAXDS (SEQ ID NO:
- 5) substitution in VRVII,
- (e) NA in VRI;
- and SGREGDAEXXD (SEQ ID NO:
- 6) in VRVII,
- (f) a Q to A substitution in loop I;
- and EDATENXIXXDR (SEQ ID NO:
- 4) in VRVII,
- (g) a Q to A substitution in loop I;
- a K to T substitution in VRV;
- and EDATENXIXXDR (SEQ ID NO:
- 4) in VRVII, and
- (h) a S to W substitution at position 267;
- and EDATENXIXXDR (SEQ ID NO:
- 4) in VRVII;
- wherein X may be any amino acid.
A variant recombinant AAV2 capsid protein comprising any one of the following sets of sequences and/or substitutions:
- (a) NA in VRI;
- a F at position 444;
- and DEAXSEXKXTXR (SEQ ID NO:
- 7) in VRIV,
- (b) Q325K in VRII;
- Y444F;
- S452A, T454N and T455V in VRIV;
- and K527R, E530D and E531D in VRVI,
- (c) Q263A in VRI;
- K490T, S492P, E499D and Y500F in VRV;
- and E530D in VRVI,
- (d) NA in VRI;
- Y444F;
- P451A, T454N, T455V and R459T in VRIV;
- and RXXDD (SEQ ID NO:
- 8) in VRVI,
- (e) E530D in VRVI,
- (f) QDXE (SEQ ID NO:
- 9), and substitutions Y500F and T503P in VRV, and
- (g) EA in VRI;
- T491V and Y500F in VRV;
- and AAADDXEXDG (SEQ ID NO:
- 10) in VRVII;
- wherein X may be any amino acid.
3-35. (canceled)
A variant recombinant adeno-associated virus (rAAV) serotype 2 (AAV2) capsid protein comprising one or more of the following sequences in the variable regions (VRs) of SEQ ID NO 29:
- (a) XX in VRI;
- QDXE in VRV;
- Y500F;
- and T503P,
- (b) XX in VRI;
- Y444F;
- SD, ID, and/or NXM in VRIV;
- S492A;
- DF in VRV;
- and DG in VRVI,
- (c) XX and/or X in VRI;
- Y444F;
- T450D;
- T454S;
- MXTXR in VRIV;
- T491V;
- Y500F;
- and E531D,
- (d) NA in VRI;
- DGE and DF in variable VRV;
- and Q545E,
- (e) DAXXT in VRI;
- Y444F;
- AXMXKXH (SEQ ID NO:
- 30) in VRIV;
- YN in VRV;
- Y500F;
- K507T;
- and DXR in VRIV,
- (f) Y444F;
- GAXNMXTXAXR (SEQ ID NO:
- 31) in VRIV;
- TXP and DF in variable VRV;
- and E530D,
- (g) XX in VRI;
- T491V;
- Y500F;
- and AAADDXEXDG (SEQ ID NO:
- 10) in VRVII,
- (h) XX in VRI;
- E530D;
- and AGRADIXXXS (SEQ ID NO:
- 33) in VRVII,
- (′) XX and/or X in VRI;
- QDXE in VRV;
- Y500F;
- T503P;
- and SAAGADXAXDS (SEQ ID NO:
- 5) in VRVII,
- (j) Q545E,
- (k) NA in VRI;
- Y500F;
- T503P;
- and K507T,
- (l) Q263A;
- Y444F;
- P451A;
- T454N;
- T455V;
- R459T;
- and RXXDD in VRVI,
- (m) Q263A and DGE and DF in variable VRV,
- (n) NA in VRI;
- and DGE and DF in variable VRV,
- (o) Q263A;
- E530D;
- E531D,
- (p) Q263A;
- DGE and DF in variable VRV;
- and SAAGADXAXDS (SEQ ID NO:
- 5) in VRVII,
- (q) NA in VRI;
- and Q545E,
- (r) GT in VRI;
- Y500F;
- K507T;
- RXXDXR in VRVI, and/or
- (s) XX in VRI;
- Y500F;
- K507T;
- RXXDXR in VRVI,
- wherein X may be any amino acid.
37-47. (canceled)
A variant recombinant adeno-associated virus (rAAV) serotype 2 (AAV2) capsid protein comprising one or more of the mutations shown in FIG. 24 or 25.
49-72. (canceled)
Dependencies are inferred from the claim text.