US 11,891,619 B2
Adeno-associated virus compositions for restoring F8 gene function and methods of use thereof
Saswati Chatterjee, Altadena, CA (US); Laura Jane Smith, Bedford, MA (US); Jeff Lynn Ellsworth, Lexington, MA (US); Hillard Rubin, Northborough, MA (US); Jason Boke Wright, Bedford, MA (US); and James Anthony McSwiggen, Arlington, MA (US)
Assigned to City of Hope, Duarte, CA (US); and Homology Medicines, Inc., Bedford, MA (US)
Filed by City of Hope, Duarte, CA (US); and Homology Medicines, Inc., Bedford, MA (US)
Filed on Mar. 10, 2022, as Appl. No. 17/654,300.
Application 17/654,300 is a division of application No. 16/279,688, filed on Feb. 19, 2019, granted, now 11,306,329.
Claims priority of provisional application 62/672,385, filed on May 16, 2018.
Claims priority of provisional application 62/632,919, filed on Feb. 20, 2018.
Claims priority of provisional application 62/632,300, filed on Feb. 19, 2018.
Prior Publication US 2022/0333138 A1, Oct. 20, 2022
Int. Cl. C12N 15/86 (2006.01); C12N 15/90 (2006.01); C12N 7/00 (2006.01)
CPC C12N 15/907 (2013.01) [C12N 7/00 (2013.01); C12N 15/86 (2013.01); C12N 2710/10042 (2013.01); C12N 2710/10043 (2013.01); C12N 2710/10061 (2013.01)] 21 Claims
 
1. A replication-defective adeno-associated virus (AAV) comprising:
a) an AAV capsid comprising an AAV Clade F capsid protein; and
b) a correction genome comprising from 5′ to 3′:
(i) a 5′ AAV ITR nucleotide sequence;
(ii) a 5′ homology arm nucleotide sequence of up to 2000 nucleotides in length, comprising a nucleotide sequence that is at least 99% identical to SEQ ID NO: 27;
(iii) an editing element for editing a target locus in the F8 gene, comprising an F8 nucleotide sequence that encodes an amino acid sequence consisting of the amino acid sequence encoded by SEQ ID NO: 26 operably linked to a polyadenylation sequence;
(iv) a 3′ homology arm nucleotide sequence of up to 2000 nucleotides in length, comprising a nucleotide sequence that is at least 99% identical to SEQ ID NO: 28; and
(v) a 3′ AAV ITR nucleotide sequence.