US 12,049,648 B2
Adeno-associated virus compositions for targeted gene therapy
Viviana Gradinaru, Pasadena, CA (US); Nicholas C. Flytzanis, Thousand Oaks, CA (US); and Nicholas S. Goeden, Thousand Oaks, CA (US)
Assigned to California Institute of Technology, Pasadena, CA (US)
Filed by California Institute of Technology, Pasadena, CA (US)
Filed on Oct. 18, 2021, as Appl. No. 17/503,972.
Application 17/503,972 is a continuation of application No. 16/582,635, filed on Sep. 25, 2019, granted, now 11,149,256.
Claims priority of provisional application 62/736,904, filed on Sep. 26, 2018.
Claims priority of provisional application 62/832,812, filed on Apr. 11, 2019.
Prior Publication US 2022/0119775 A1, Apr. 21, 2022
Prior Publication US 2024/0101969 A9, Mar. 28, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 7/00 (2006.01)
CPC C12N 7/00 (2013.01) [C12N 2750/14071 (2013.01); C12N 2750/14121 (2013.01); C12N 2750/14122 (2013.01)] 19 Claims
OG exemplary drawing
 
1. A recombinant AAV (rAAV), the rAAV comprising:
a) a variant AAV capsid comprising a variant AAV capsid protein comprising an amino acid substitution of three or more amino acids within a 7-mer peptide sequence of a parental AAV capsid protein, wherein the 7-mer peptide sequence is from amino acid positions that correspond to amino acid residues 452-458 of AAV9 VP1 (SEQ ID NO:1), and wherein the amino acid substitution is not ILGTGTS (SEQ ID NO: 45479), not QSSQTPR (SEQ ID NO: 45480), and not TLAVPFK (SEQ ID NO: 45477); and
b) a heterologous polynucleotide comprising a nucleotide sequence encoding a gene product,
wherein the variant AAV capsid has an increased tropism for a target cell or tissue, when measured in a subject, relative to a tropism of the parental AAV capsid,
wherein the target cell or tissue is selected from the group consisting of a central nervous system (CNS) cell, a peripheral nervous system (PNS) cell, lung tissue, intestinal tissue, heart tissue, stomach tissue, and a combination thereof.