Compositions and methods for treating stargardt disease
AssigneeBeam Therapeutics Inc.
InventorsJack Sullivan, David Bryson, Luis Fernando Camarillo Guerrero
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Abstract
Compositions and methods for editing a pathogenic ATP-binding cassette, subfamily A, member 4 (ABCA4) polypeptide-encoding gene using an adenosine deaminase base editor to treat a congenital eye disorder, such as Stargardt disease. In various embodiments, the disclosure provides methods for altering a nucleobase (e.g., c.4139T) in an ABCA4 gene codon 1380 encoding a pathogenic leucine so that the codon is altered to encode a proline. In some embodiments, the disclosure provides methods for altering a pathogenic c.5714+5A intronic nucleotide of anABCA4 gene so that the nucleotide becomes c.5714+5G.
Claims20
A method of editing a c.4139T nucleobase of an ATP-binding cassette, subfamily A, member 4 (ABCA4) polynucleotide in a cell, the method comprising contacting the cell with a base editor system comprising:
- (a) a base editor polypeptide comprising a nucleic acid programmable DNA binding protein (napDNAbp) domain and an adenosine deaminase domain, or one or more polynucleotides encoding the base editor, and
- (b) one or more guide polynucleotides, or one or more polynucleotides encoding the guide polynucleotides, that target said base editor to effect a deamination of the adenosine (A) complementary to the c.4139T nucleobase, thereby introducing a target c.4139T>C alteration to the ABCA4 polynucleotide.
A method of editing a c.5714+5A nucleobase of an ATP-binding cassette, subfamily A, member 4 (ABCA4) polynucleotide in a cell, the method comprising contacting the cell with a base editor system comprising:
- (a) a base editor polypeptide comprising a nucleic acid programmable DNA binding protein (napDNAbp) domain and an adenosine deaminase domain, or one or more polynucleotides encoding the base editor, and
- (b) one or more guide polynucleotides, or one or more polynucleotides encoding the guide polynucleotides, that target said base editor to effect a deamination of the c.5714+5A nucleobase, thereby introducing a target c.5714+5A>G alteration to the ABCA4 polynucleotide.
A base editor system comprising:
- (a) a base editor polypeptide comprising a nucleic acid programmable DNA binding protein (napDNAbp) domain and an adenosine deaminase domain, or one or more polynucleotides encoding the base editor, and
- (b) one or more guide polynucleotides, or one or more polynucleotides encoding the one or more guide polynucleotides, that target said base editor to effect a deamination of the adenosine (A) complementary to a c.4139T nucleobase of a ATP-binding cassette, subfamily A, member 4 (ABCA4) polynucleotide.
A base editor system comprising:
- (a) a base editor polypeptide comprising a nucleic acid programmable DNA binding protein (napDNAbp) domain and an adenosine deaminase domain, or one or more polynucleotides encoding the base editor, and
- (b) one or more guide polynucleotides, or one or more polynucleotides encoding the one or more guide polynucleotides, that target said base editor to effect a deamination of a c.5714+5A nucleobase of a ATP-binding cassette, subfamily A, member 4 (ABCA4) polynucleotide.
A guide polynucleotide comprising a spacer with a sequence comprising at least 10 contiguous nucleotides sequences selected from those sequences listed in Table 1 or Table 2.
Dependencies are inferred from the claim text.