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US 10,113,163 B2Granted
Adenosine nucleobase editors and uses thereof
AssigneePresident and Fellows of Harvard College
InventorsDavid R. Liu, Nicole Gaudelli
Life of this patent
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Abstract
The disclosure provides adenosine deaminases that are capable of deaminating adenosine in DNA. The disclosure also provides fusion proteins comprising a Cas9 (e.g., a Cas9 nickase) domain and adenosine deaminases that deaminate adenosine in DNA. In some embodiments, the fusion proteins further comprise a nuclear localization sequence (NLS), and/or an inhibitor of base repair, such as, a nuclease dead inosine specific nuclease (dISN).
Claims32
An adenosine deaminase comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs:
- 1, 8, 9, 371, 372, 373, 374, or 375 with the exception of one or more substitutions at positions selected from the group consisting of amino acid residues corresponding to positions 8, 17, 18, 23, 34, 36, 45, 48, 51, 56, 59, 84, 85, 94, 95, 102, 104, 106, 107, 108, 110, 118, 123, 127, 138, 142, 146, 147, 149, 151, 152, 153, 154, 155, 156, and 157 of the amino acid sequence of SEQ ID NO:
- 1, wherein said adenosine deaminase deaminates adenine in deoxyribonucleic acid (DNA).
Dependencies are inferred from the claim text.