The Wild-Type tRNA Adenosine Deaminase Enzyme TadA Is Capable of Sequence-Specific DNA Base Editing.

ABSTRACT: Base editors are genome editing tools that enable site-specific base conversions through the chemical modification of nucleobases in DNA. Adenine base editors (ABEs) convert A ⋅ T to G ⋅ C base pairs in DNA by using an adenosine deaminase enzyme to modify target adenosines to inosine intermediates. Due to the lack of a naturally occurring adenosine deaminase that can modify DNA, ABEs were evolved from a tRNA-deaminating enzyme, TadA. Previous experiments with an ABE comprising a wild-type (wt) TadA showed no detectable activity on DNA, and directed evolution was therefore required to enable this enzyme to accept DNA as a substrate. Here we show that wtTadA can perform base editing in DNA in both bacterial and mammalian cells, with a strict sequence motif requirement of TAC. We leveraged th

SUBMITTER: Ranzau BL 

PROVIDER: S-EPMC10514239 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature