Gene therapy for the treatment of ht1
AssigneeLogicBio Therapeutics, Inc.
InventorsQiang Xiong, Chih-Wei Ko
Life of this patent
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Abstract
The present disclosure provides compositions and methods for gene therapy. Further, the present disclosure provides compositions and methods for treatment of HT1 through novel gene therapy mechanisms.
Claims33
A composition comprising:
- a closed circular cDNA integrating gene therapy construct comprising, from 5′ to 3′, a polynucleotide sequence encoding (a) a 5′ homology arm between 1 kb and 1.6 kb in length, (b) a P2A coding sequence encoding a P2A peptide, (c) a therapeutic payload, and (d) a 3′ homology arm between 1 kb and 1.6 kb in length, wherein:
- the therapeutic payload comprises a transgene sequence encoding fumarylacetoacetate hydrolase (FAH);
- and
- the homology arm sequences promote integration of the construct at an endogenous albumin target site such that the albumin locus can result in the simultaneous production of albumin-2A and the transgene as separate proteins.
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-34. (canceled)
A closed circular DNA consisting of the polynucleotide sequence of SEQ ID NO:
- 23, the polynucleotide sequence of SEQ ID NO:
- 24, the polynucleotide sequence of SEQ ID NO:
- 25, or the polynucleotide sequence of SEQ ID NO:
- 26.
36-38. (canceled)
A liver-targeted, recombinant AAV vector for treating HT1 and encoding a human FAH, the liver-targeted recombinant AAV vector comprising a closed, circular cDNA polynucleotide sequence comprising:
- a human FAH polynucleotide sequence encoding a functional FAH transgene comprising the nucleotide sequence of SEQ ID NO:
- 20, SEQ ID NO:
- 21, or SEQ ID NO:
- 22, preceded by a 2A-peptide sequence encoding a 2A-peptide comprising the amino acid sequence of SEQ ID NO:
- 7;
- the human FAH polynucleotide sequence and 2A-peptide sequence together flanked by a 3′ homology arm comprising the nucleotide sequence of SEQ ID NO:
- 2;
- and a 5′ homology arm comprising the nucleotide sequence of SEQ ID NO:
- 1 or SEQ ID NO:
- 3.
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A method of treating HT1 comprising administering to a subject in need thereof a therapeutically effective dose of a liver-targeted, recombinant AAV vector encoding human FAH, the liver-targeted, recombinant AAV vector comprising a cDNA polynucleotide sequence comprising
- a FAH polynucleotide sequence encoding a functional human FAH, the FAH polynucleotide sequence comprising the nucleotide sequence of SEQ ID NO:
- 20, SEQ ID NO:
- 21, or SEQ ID NO:
- 22, preceded by a 2A-peptide sequence encoding a 2A-peptide comprising the amino acid sequence of SEQ ID NO:
- 7;
- the FAH polynucleotide sequence and 2A-peptide sequence together flanked by a 3′ homology arm comprising the nucleotide sequence of SEQ ID NO:
- 2;
- and a 5′ homology arm comprising the nucleotide sequence of SEQ ID NO:
- 1, or SEQ ID NO:
- 3.
Dependencies are inferred from the claim text.