Unintended DNA Changes Caused by CRISPR Base Editors

DNA base editors can cause substantial off-target editing in both genomic DNA and RNA.

• Base editing induces specific single-nucleotide changes within genomic DNA without creating double-strand breaks.
• Cytosine and adenine base editors consist of a Cas9 protein linked to a deaminase enzyme directed by a guide RNA.
• Recent studies indicate that off-target editing is primarily independent of guide RNA.
• The off-target activity is associated with the promiscuous reactivity of the deaminase enzymes used in base editing.
• Strategies exist to improve the selectivity of DNA base editors.

Simplified