Adeno-associated virus (AAV) delivery of anti-FAM19A5 antibodies
The present disclosure provides adeno-associated vims (AAV) vectors and uses thereof. In certain embodiments, the AAV vectors comprise a nucleic acid that encodes an antagonist against a family with sequence similarity 19, member A5 (FAM19A5) protein, e.g., anti-FAM19A5 antibody, e.g., anti-FAM19A5 scFv.
1. An adeno-associated virus (AAV) vector comprising a nucleic acid that encodes an antibody, or an antigen-binding portion thereof, which specifically binds to a family with sequence similarity 19, member A5 (FAM19A5) protein (anti-FAM19A5 antibody), wherein the anti-FAM19A5 antibody comprises a heavy chain CDR1, CDR2, and CDR3 and a light chain CDR1, CDR2, and CDR3, and wherein:
(i) the heavy chain CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 16;
(ii) the heavy chain CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 212;
(iii) the heavy chain CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 213;
(iv) the light chain CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 222;
(v) the light chain CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 225; and
(vi) the light chain CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 224.
2. The AAV vector of claim 1 , further comprising an intron, a signal peptide, one or more adeno-associated virus inverted terminal repeats (ITRs), or any combination thereof.
3. The AAV vector of claim 1 , wherein the anti-FAM19A5 antibody comprises a Fab, a Fab′, a F (ab′)2, a Fv, a single chain Fv (scFv), or a combination thereof.
4. The AAV vector of claim 3 , wherein the anti-FAM19A5 antibody is a scFv.
5. The AAV vector of claim 1 , wherein the nucleic acid is codon optimized.
6. An adeno-associated virus (AAV) vector comprising a nucleic acid that encodes an antibody, or an antigen-binding portion thereof, which specifically binds to a family with sequence similarity 19, member A5 (FAM19A5) protein (anti-FAM19A5 antibody), wherein the nucleic acid comprises the nucleotide sequence set forth in SEQ ID NO: 204, or SEQ ID NO: 301.
7. An adeno-associated virus (AAV) vector comprising a nucleic acid that encodes an antibody, or an antigen-binding portion thereof, which specifically binds to a family with sequence similarity 19, member A5 (FAM19A5) protein (anti-FAM19A5 antibody), wherein the scFv comprises the amino acid sequence set forth in SEQ ID NO: 201 or SEQ ID NO: 256.
8. The AAV vector of claim 1 , wherein the anti-FAM19A5 antibody comprises
a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 236 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 245.
9. The AAV vector of claim 1 , wherein the anti-FAM19A5 antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence which is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 236; and/or wherein the light chain variable region comprises an amino acid sequence which is at least about 80% identical to the amino acid sequence set forth in SEQ ID NO: 245.
10. The AAV vector of claim 1 , wherein: (i) the anti-FAM19A5 antibody, or antigen-binding portion thereof, is capable of inhibiting the binding of a reference antibody, or antigen-binding portion thereof, to a human FAM19A5 protein by at least about 10%, as measured by a binding inhibition assay; (ii) the anti-FAM19A5 antibody, or antigen-binding portion thereof, is capable of reducing a concentration of FAM19A5 protein in a culture medium comprising an astrocyte cell line by at least about 10%, as measured by ELISA; or (iii) both (i) and (ii).
11. A composition comprising the AAV vector of claim 1 and a carrier.
12. An isolated host cell comprising the AAV vector of claim 1 .
13. The AAV vector of claim 6 , wherein the nucleic acid comprises the nucleotide sequence set forth in SEQ ID NO: 301.
14. A composition comprising the AAV vector of claim 13 and a carrier.
15. A composition comprising the AAV vector of claim 7 and a carrier.
16. An isolated host cell comprising the AAV vector of claim 7 .
17. A composition comprising the AAV vector of claim 8 and a carrier.
18. An isolated host cell comprising the AAV vector of claim 8 .
19. A composition comprising the AAV vector of claim 9 and a carrier.
20. An isolated host cell comprising the AAV vector of claim 9 .