Adenosine nucleobase editors and uses thereof
AssigneePresident and Fellows of Harvard College
InventorsDavid R. Liu, Nicole Gaudelli
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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).
Claims21
An adenosine deaminase comprising an amino acid sequence having at least 85% amino acid sequence identity to the amino acid sequence of SEQ ID NO:
- 1, with the exception of one or more of the following substitutions H36L, P48A, L84F, A106V, D108N, S146C, S146R, R152P, E155V, I156F, and K157N in the amino acid sequence of SEQ ID NO:
- 1, and wherein said adenosine deaminase deaminates adenine in deoxyribonucleic acid (DNA).
An adenosine deaminase comprising an amino acid sequence having at least 85% amino acid sequence identity to the amino acid sequence of SEQ ID NO:
- 1, with the exception of the following amino acid substitutions H36L, P48A, L84F, A106V, D108N, S146C or S146R, R152P, E155V, I156F, and K157N in the amino acid sequence of SEQ ID NO:
- 1, and wherein said adenosine deaminase deaminates adenine in deoxyribonucleic acid (DNA).
An adenosine deaminase comprising an amino acid sequence having at least 85% amino acid sequence identity to the amino acid sequence of SEQ ID NO:
- 1, with the exception of the following amino acid substitutions H36L, P48A, L84F, A106V, D108N, S146C or S146R, R152P, E155V, I156F, and K157N, and one or more substitutions at positions selected from the group consisting of amino acid residues corresponding to positions 123, 147, 154, and 166 in the amino acid sequence of SEQ ID NO:
- 1, wherein said adenosine deaminase variant deaminates adenine in deoxyribonucleic acid (DNA).
Dependencies are inferred from the claim text.