Adeno-associated virus compositions for pah gene transfer and methods of use thereof
AssigneeHomology Medicines, Inc.
InventorsAlbert Barnes Seymour, Seemin Seher Ahmed, Jason Boke Wright, Serena Nicole Dollive, Hillard Rubin
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Abstract
Provided herein are adeno-associated virus (AAV) compositions that can express a phenylalanine hydroxylase (PAH) polypeptide in a cell, thereby restoring the PAH gene function. Also provided are methods of use of the AAV compositions, and packaging systems for making the AAV compositions.
Claims22
1-28. (canceled)
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 1 (HCR1) and a human al-antitrypsin (hAAT) promoter;
- (c) a silently altered PAH coding sequence encoding the amino acid sequence set forth in SEQ ID NO:
- 23;
- and
- (d) an AAV2 3′ ITR nucleotide sequence.
The AAV genome of claim 1, wherein the 5′ ITR nucleotide sequence has at least 95% sequence identity to the nucleotide sequence of SEQ ID NO:
- 26, and the 3′ ITR nucleotide sequence has at least 95% sequence identity to the nucleotide sequence of SEQ ID NO:
- 27.
The AAV genome of claim 1, wherein the 5′ ITR nucleotide sequence has the nucleotide sequence of SEQ ID NO:
- 26, and the 3′ ITR nucleotide sequence has the nucleotide sequence of SEQ ID NO:
- 27.
The AAV genome of claim 1, wherein the silently altered PAH coding sequence has at least 80% sequence identity to the nucleotide sequence of SEQ ID NO:
- 71.
A replication-defective AAV comprising:
- an AAV capsid comprising a capsid protein;
- and an AAV genome of claim 1.
Dependencies are inferred from the claim text.