Journal of cellular and molecular medicineApr 25, 2026

Improvements in CRISPR Base Editing: From Molecular Changes to Medical Treatments

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Apr 26, 2026

Abstract

Base editing enables targeted single-nucleotide conversions without DNA double-strand breaks or donor templates.

Base editors fuse inactive Cas proteins with DNA deaminase enzymes to perform precise genetic modifications.
Cytosine base editors convert C•G to T•A pairs, while adenine base editors change A•T to G•C.
These editors utilize the R-loop structure formed by Cas binding and leverage natural DNA repair processes.
Challenges such as off-target effects, bystander edits, and delivery methods remain significant concerns.
Continuous engineering has improved accuracy, expanded targetability, and reduced unwanted edits in base editing tools.
Preclinical studies have successfully corrected mutations linked to diseases, leading to ongoing clinical trials for various conditions.

Simplified

CRISPR-Cas9 systems revolutionized gene editing, but inherent drawbacks, namely DNA double-strand breaks (DSBs) and the difficulty of achieving precise repairs (due to low HDR efficiency), led researchers to invent new, more accurate gene editing tools. Base editing represents a significant leap forward, enabling targeted single-nucleotide conversions directly on the DNA without DSBs or donor templates. The core technology involves fusing catalytically dead or nickase Cas proteins to DNA deaminase enzymes. Cytosine base editors (CBEs) convert C•G to T•A pairs, while adenine base editors (ABEs) change A•T to G•C. These editors exploit the deaminase function within the R-loop structure formed by Cas binding and co-opt endogenous DNA repair mechanisms for precision. While offering improved efficiency and editing precision, base editing faces persistent challenges, such as off-target effects, bystander edits, delivery and ethical concerns. Continuous engineering efforts have refined these tools, enhancing accuracy, expanding targetability and reducing unwanted edits. The base editing arsenal has also broadened to include C-to-G base editors (CGBEs), dual A&C editors and versions targeting organelles. Successful preclinical studies demonstrating the correction of mutations responsible for the disease have paved the way for clinical trials, which are now testing therapies for conditions like sickle cell disease, β-thalassaemia and hypercholesterolemia using various delivery systems. This review explores CRISPR base editing's origins, mechanisms of action, potential therapies and current restrictions, pointing to its broadening impact on medical genetics.

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The authors declare no conflicts of interest.

PubMed

Improvements in CRISPR Base Editing: From Molecular Changes to Medical Treatments

Abstract

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Funding

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Abstract

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Funding

Competing interests

Related papers

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the crispr gene editing brief