Hyperactive Nickase Activity Improves Adenine Base Editing

Sep 19, 2024ACS synthetic biology

Increased Nickase Activity Improves Adenine Base Editing

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Abstract

TurboABE demonstrates enhanced editing efficiency on adenine target sites without increasing off-target effects.

TurboABE is a modified adenine base editor that utilizes a TurboCas9 nickase to enhance genome editing.
The technology shows improved editing rates at adenine bases that are typically difficult to edit.
Editing efficiency is amplified across various adenine target sequences.
No increase in off-target editing was observed in both DNA and RNA.

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Base editing technologies enable programmable single-nucleotide changes in target DNA without double-stranded DNA breaks. Adenine base editors (ABEs) allow precise conversion of adenine (A) to guanine (G). However, limited availability of optimized deaminases as well as their variable efficiencies across different target sequences can limit the ability of ABEs to achieve effective adenine editing. Here, we explored the use of a TurboCas9 nickase in an ABE to improve its genome editing activity. The resulting TurboABE exhibits amplified editing efficiency on a variety of adenine target sites without increasing off-target editing in DNA and RNA. An interesting feature of TurboABE is its ability to significantly improve the editing frequency at bases with normally inefficient editing rates in the editing window of each target DNA. Development of improved ABEs provides new possibilities for precise genetic modification of genes in living cells.

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Hyperactive Nickase Activity Improves Adenine Base Editing

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