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US 2019/0231901 A1Published application
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.
Claims28
A replication-defective adeno-associated virus (AAV) comprising:
- (a) an AAV capsid comprising an AAV Clade F capsid protein;
- and
- (b) a transfer genome comprising a silently altered PAH coding sequence, wherein the silently altered PAH coding sequence comprises the nucleotide sequence set forth in SEQ ID NO:
- 25.
1 more element
A replication-defective AAV comprising:
- (a) an AAV capsid comprising:
- an AAV capsid protein comprising an amino acid sequence having at least 95% sequence identity with the amino acid sequence of amino acids 203-736 of SEQ ID NO:
- 16, wherein the amino acid in the capsid protein corresponding to amino acid 346 of SEQ ID NO:
- 16 is A, and wherein the amino acid in the capsid protein corresponding to amino acid 505 of SEQ ID NO:
- 2 is R;
- a capsid protein comprising an amino acid sequence having at least 95% sequence identity with the amino acid sequence of amino acids 138-736 of SEQ ID NO:
- 16, wherein the amino acid in the capsid protein corresponding to amino acid 346 of SEQ ID NO:
- 16 is A, and wherein the amino acid in the capsid protein corresponding to amino acid 505 of SEQ ID NO:
- 2 is R;
- and/or
- a capsid protein comprising an amino acid sequence having at least 95% sequence identity with the amino acid sequence of amino acids 1-736 of SEQ ID NO:
- 16, wherein the amino acid in the capsid protein corresponding to amino acid 346 of SEQ ID NO:
- 16 is A, and wherein the amino acid in the capsid protein corresponding to amino acid 505 of SEQ ID NO:
- 2 is R;
- and
- (b) a transfer genome comprising the nucleotide sequence set forth in SEQ ID NO:
- 47.
14 more elements
A replication-defective AAV comprising:
- (a) an AAV capsid comprising:
- an AAV capsid protein comprising an amino acid sequence having at least 95% sequence identity with the amino acid sequence of amino acids 203-736 of SEQ ID NO:
- 16, wherein the amino acid in the capsid protein corresponding to amino acid 346 of SEQ ID NO:
- 16 is A, and wherein the amino acid in the capsid protein corresponding to amino acid 505 of SEQ ID NO:
- 2 is R;
- a capsid protein comprising an amino acid sequence having at least 95% sequence identity with the amino acid sequence of amino acids 138-736 of SEQ ID NO:
- 16, wherein the amino acid in the capsid protein corresponding to amino acid 346 of SEQ ID NO:
- 16 is A, and wherein the amino acid in the capsid protein corresponding to amino acid 505 of SEQ ID NO:
- 2 is R;
- and/or
- a capsid protein comprising an amino acid sequence having at least 95% sequence identity with the amino acid sequence of amino acids 1-736 of SEQ ID NO:
- 16, wherein the amino acid in the capsid protein corresponding to amino acid 346 of SEQ ID NO:
- 16 is A, and wherein the amino acid in the capsid protein corresponding to amino acid 505 of SEQ ID NO:
- 2 is R;
- and
- (b) a transfer genome comprising the nucleotide sequence set forth in SEQ ID NO:
- 52.
14 more elements
A polynucleotide comprising the nucleotide sequence set forth in SEQ ID NO:
- 25, 47 or 52.
Dependencies are inferred from the claim text.