Base Editing

Base editing converts one DNA base to another without double-strand breaks. A catalytically impaired Cas9 is fused to a deaminase that chemically modifies a target base, which cellular repair then resolves into a permanent change.

Because it avoids cutting the DNA backbone, base editing produces fewer indels and chromosomal rearrangements than conventional CRISPR. It excels at correcting point mutations — the cause of roughly half of all known human genetic diseases.

Limitations include restricted conversion scope (only four of twelve possible changes), bystander edits at nearby bases, and off-target RNA editing. It is also constrained by the requirement for a suitable PAM sequence near the target.

Base editing treats the genome as a text to be edited letter by letter. Whether this metaphor is accurate or dangerously misleading depends on whether we remember that genomes are dynamic networks, not static manuscripts.