AAV CAPSIDS COMPRISING ANTITRANSFERRIN ANTIBODY DOMAINS

Claims

This description relates to targeted fragments (e.g., CNS-targeted fragments) comprising single-stranded antibody agents that can be inserted into the capsid of a recombinant adeno-associated virus (rAAV) vector. Also described herein are compositions comprising the CNS-targeted fragments described herein and methods for their preparation and use.

1. A recombinant adeno-associated virus (rAAV) particle comprising: (a) an AAV capsid protein variant comprising a single-stranded antibody agent that binds to a transferrin receptor (TfR1) or a variant or fragment thereof, wherein the single-stranded antibody agent is inserted into a variable region (VR) of an original AAV capsid protein, and (b) a heterologous nucleic acid comprising a nucleotide sequence encoding an active payload.

54. A pharmaceutical composition comprising: (a) an rAAV particle of any of the preceding claims; and (b) a pharmaceutically acceptable excipient.

60. An isolated cell with rAAV particle transduction of any of claims 1 to 53.

61. An isolated nucleic acid comprising a nucleotide sequence encoding a variant of the AAV capsid protein, wherein the variant of the AAV capsid protein comprises a single-stranded antibody agent that binds to a transferrin receptor (TfR) or a variant or fragment thereof, and wherein the single-stranded antibody agent is inserted into a variable region (VR) of an original AAV capsid protein.

62. An isolated cell comprising the nucleic acid of claim 61.

63. An AAV capsid protein variant, wherein the AAV capsid protein variant comprises a single-chain antibody agent that binds to a transferrin receptor (TfR) or a variant or fragment thereof, and wherein the single-chain antibody agent is inserted into a variable region (VR) of an original AAV capsid protein.