	US 12,064,486 B2
	Adeno-associated virus compositions for PAH gene transfer and methods of use thereof
Albert Barnes Seymour, Westborough, MA (US); Seemin Seher Ahmed, Worcester, MA (US); Jason Boke Wright, Concord, MA (US); Serena Nicole Dollive, Waltham, MA (US); and Hillard Rubin, Northborough, MA (US)
Assigned to Homology Medicines, Inc., Bedford, MA (US)
Filed by HOMOLOGY MEDICINES, INC., Bedford, MA (US)
Filed on Feb. 24, 2020, as Appl. No. 16/798,890.
Application 16/798,890 is a continuation of application No. 16/369,879, filed on Mar. 29, 2019, granted, now 10,610,606.
Application 16/369,879 is a continuation of application No. PCT/US2019/016351, filed on Feb. 1, 2019.
Prior Publication US 2020/0289674 A1, Sep. 17, 2020
Int. Cl. C12N 15/864 (2006.01); A61K 38/43 (2006.01); A61K 48/00 (2006.01); C12N 15/11 (2006.01); C12N 15/52 (2006.01); C12N 15/86 (2006.01)

CPC A61K 48/0066 (2013.01) [C12N 15/86 (2013.01); C12N 2750/14143 (2013.01); C12N 2750/14152 (2013.01); C12N 2750/14171 (2013.01); C12N 2830/32 (2013.01)]

20 Claims

1. An adeno-associated virus (AAV) genome comprising, from 5′ to 3′: (a) an AAV2 5′ inverted terminal repeat (ITR) nucleotide sequence; (b) a transcriptional regulatory element comprising, from 5′ to 3′, a human hepatic control region | (HCR1) and a human a1-antitrypsin (hAAT) promoter; (c) a silently altered phenylalanine hydroxylase (PAH) coding sequence having at least 80% sequence identity to the nucleotide sequence of SEQ ID NO: 71, wherein the silently altered PAH coding sequence encodes the amino acid sequence set forth in SEQ ID NO: 23; and (d) an AAV2 3′ ITR nucleotide sequence.