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RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...

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Updated: Mar 20, 2026

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Published on: February 28, 2021

Precise, minimally evolved adenine base editors generated through mutation reversion analysis.

Mallory Evanoff¹, Sanjana Korpal¹, Zachary D Krill¹

¹Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA.

Nature Biotechnology

|March 19, 2026

Summary

This summary is machine-generated.

Researchers engineered adenine base editors (ABEs) for precise genome editing. Minimally evolved ABEs (ME-ABEs) show enhanced on-target activity and reduced off-target effects, improving therapeutic applications.

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A Nonsequencing Approach for the Rapid Detection of RNA Editing

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Published on: April 21, 2022

Area of Science:

Molecular Biology
Genome Engineering
Biotechnology

Background:

Adenine base editors (ABEs) enable A•T to G•C conversions in the genome.
The first ABE, ABE7.10, was developed using directed evolution on 14 mutations in the TadA deaminase.
Understanding mutation impacts is crucial for improving ABE efficiency and precision.

Purpose of the Study:

To analyze the impact of mutations on TadA fitness.
To engineer more efficient and precise adenine base editors.
To develop minimally evolved ABEs (ME-ABEs) with improved characteristics.

Main Methods:

Comprehensive reversion analysis of TadA mutations.
Activity assessment in human and Escherichia coli host systems.
Categorization of mutations based on host-dependent fitness.

Main Results:

Up to five mutations can be reverted to generate ME-ABEs.
ME-ABEs exhibit narrow editing windows, similar to ABE7.10.
ME-ABEs demonstrate enhanced on-target editing and low off-target activity, comparable to ABE8e and ABE8.20.
ME-ABEs successfully edited challenging clinical sites.

Conclusions:

Minimally evolved ABEs offer a balance of efficiency, precision, and reduced off-target effects.
ME-ABEs represent a significant advancement in base editing technology.
These findings facilitate the development of safer and more effective gene therapies.