	US 12,076,420 B2
	Adeno-associated virus compositions for restoring PAH gene function and methods of use thereof
Jason Boke Wright, Bedford, MA (US); Danielle Lauren Sookiasian, Bedford, MA (US); Thia Baboval St. Martin, Bedford, MA (US); Omar Francone, Bedford, MA (US); and Albert Barnes Seymour, Bedford, MA (US)
Assigned to Homology Medicines, Inc., Bedford, MA (US)
Filed by Homology Medicines, Inc., Bedford, MA (US)
Filed on May 27, 2021, as Appl. No. 17/303,343.
Claims priority of provisional application 63/117,252, filed on Nov. 23, 2020.
Claims priority of provisional application 63/030,341, filed on May 27, 2020.
Prior Publication US 2021/0393804 A1, Dec. 23, 2021
Int. Cl. C12N 15/864 (2006.01); A61K 38/44 (2006.01); A61K 48/00 (2006.01); C12N 15/12 (2006.01); C12N 15/86 (2006.01); C12N 15/90 (2006.01)

CPC A61K 48/0066 (2013.01) [A61K 38/44 (2013.01); C12N 15/86 (2013.01); C12N 2750/14143 (2013.01); C12N 2750/14151 (2013.01); C12N 2830/50 (2013.01); C12Y 114/16001 (2013.01)]

18 Claims

1. A recombinant adeno-associated virus (rAAV) comprising: (a) an AAV capsid comprising an AAV capsid protein; and (b) an rAAV genome comprising: (1) an editing element for editing a target locus in a phenylalanine hydroxylase (PAH) gene, comprising a PAH coding sequence operably linked to a transcriptional regulatory element, wherein the PAH coding sequence comprises the nucleotide sequence set forth in SEQ ID NO: 28; (ii) a 5′ homology arm nucleotide sequence positioned 5′ of the editing element, having homology to a first genomic region 5′ to the target locus; and (iii) a 3′ homology arm nucleotide sequence positioned 3′ of the editing element, having homology to a second genomic region 3′ to the target locus.