Article
Directed evolution of adenine base editors with increased activity and therapeutic application.
Nature biotechnology - 1 Jul 2020
Gaudelli Nicole M, Lam Dieter K, Rees Holly A, Solá-Esteves Noris M, Barrera Luis A, Born David A, Edwards Aaron, Gehrke Jason M, Lee Seung-Joo, Liquori Alexander J, Murray Ryan, Packer Michael S, Rinaldi Conrad, Slaymaker Ian M, Yen Jonathan, Young Lauren E, Ciaramella Giuseppe
Abstract excerpt
The foundational adenine base editors (for example, ABE7.10) enable programmable A•T to G•C point mutations but editing efficiencies can be low at challenging loci in primary human cells. Here we further evolve ABE7.10 using a library of adenosine deaminase variants to create ABE8s. At NGG protospacer adjacent motif (PAM) sites, ABE8s result in ~1.5× higher editing at protospacer positions A5-A7 and ~3.2× higher...
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