Methods of treating phenylketonuria
AssigneeHomology Medicines, Inc.
InventorsOmar L. Francone, Deborah A. Kinch, Diana Lamppu, Albert Barnes Seymour, Teresa Leah Wright
Life of this patent
Estimating the term…
Abstract
Provided herein are methods of treating a subject having a disease or disorder associated with a PAH gene mutation. The methods generally comprise administering to the subject a therapeutically effective does of a recombinant adeno-associated virus (rAAV) that can express a phenylalanine hydroxylase (PAH) polypeptide in a cell and thereby restore PAH gene function in the subject.
Claims17
A method for treating a subject having phenylketonuria (PKU), the method comprising administering to the subject an rAAV at a dose of about 6e13 vg/kg to about 1e14 vg/kg, wherein the rAAV comprises:
- (a) an AAV capsid comprising:
- a 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:11, wherein the amino acid in the capsid protein corresponding to amino acid 346 of SEQ ID NO:11 is A, and wherein the amino acid in the capsid protein corresponding to amino acid 505 of SEQ ID NO:11 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:11, wherein the amino acid in the capsid protein corresponding to amino acid 346 of SEQ ID NO:11 is A, and wherein the amino acid in the capsid protein corresponding to amino acid 505 of SEQ ID NO:11 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:11, wherein the amino acid in the capsid protein corresponding to amino acid 346 of SEQ ID NO:11 is A, and wherein the amino acid in the capsid protein corresponding to amino acid 505 of SEQ ID NO:11 is R;
- and
- (b) a transfer genome comprising a silently altered PAH coding sequence operably linked to a transcriptional regulatory element, wherein the silently altered PAH coding sequence comprises a nucleotide sequence having at least 95% sequence identity to the sequence set forth in SEQ ID NO:
- 1, and encodes the amino acid sequence set forth in SEQ ID NO:13.
A method for treating a subject having PKU, the method comprising intravenously administering to the subject an rAAV at a dose of about 6e13 vg/kg, about 8e13 vg/kg, or about 1e14 vg/kg, wherein the rAAV comprises:
- (a) an AAV capsid comprising:
- a 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:11, wherein the amino acid in the capsid protein corresponding to amino acid 346 of SEQ ID NO:11 is A, and wherein the amino acid in the capsid protein corresponding to amino acid 505 of SEQ ID NO:11 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:11, wherein the amino acid in the capsid protein corresponding to amino acid 346 of SEQ ID NO:11 is A, and wherein the amino acid in the capsid protein corresponding to amino acid 505 of SEQ ID NO:11 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:11, wherein the amino acid in the capsid protein corresponding to amino acid 346 of SEQ ID NO:11 is A, and wherein the amino acid in the capsid protein corresponding to amino acid 505 of SEQ ID NO:11 is R;
- and
- (b) a transfer genome comprising the nucleotide sequence set forth in SEQ ID NO:7 or SEQ ID NO:10.
Dependencies are inferred from the claim text.