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Assignee4D Molecular Therapeutics Inc.
InventorsDavid H. KIRN, Melissa KOTTERMAN, David SCHAFFER
Estimating the term…
Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of retinal cells as compared to the infectivity of the retinal cells by an AAV virion comprising the unmodified parental AAV capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and in clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more cells of the retina for the treatment of retinal disorders and diseases.
A method for treating a human subject with choroideremia, the method comprising administering a therapeutically effective amount of an infectious recombinant adeno-associated virus (rAAV) particle, the rAAV particle comprising (i) a capsid comprising a capsid protein comprising a heterologous peptide with a length of 7-11 amino acids covalently inserted between amino acids corresponding to amino acids 587 and 588 of VP1 of AAV2 (SEQ ID NO:2) or the corresponding position in the capsid protein of another AAV serotype, the peptide insertion comprising the amino acid sequence ISDQTKH (SEQ ID NO:14) and having from 1 to 3 spacer amino acids (Y1-Y3) at the amino and/or carboxyl terminus of amino acid sequence ISDQTKH (SEQ ID NO:14) and (ii) a nucleic acid comprising a nucleotide sequence encoding a Rab escort protein-1 (REP1), said nucleotide sequence operably linked to an expression control sequence, or administering a pharmaceutical composition comprising said infectious rAAV particle and a pharmaceutically acceptable excipient.
A method for treating a human subject with choroideremia, the method comprising administering by intravitreal injection a therapeutically effective amount of an rAAV particle, said rAAV particle comprising (i) a capsid comprising a capsid protein comprising the amino acid sequence set forth as SEQ ID NO:42 and (ii) a heterologous nucleic acid comprising nucleotide sequence encoding a REP1, said nucleotide sequence operably linked to a CAG promoter.
Dependencies are inferred from the claim text.