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New gene editing tools could become gamechangers for gene therapy, but scientists need to develop new approaches that curtail undesirable mutations. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system is one such error-prone editing tool that scientists later modified to limit its mutational burden.However, it’s unclear how the adapted techniques, called base and prime editing, stack up against the original CRISPR-Cas9 system.2 Reporting in the journal Nature Biotechnology, researchers at the San Raffaele Scientific Institute revealed that base and prime editing produced more mutations than previously suggested but produced them less often than CRISPR-Cas9.

CRISPR-Cas9 gene editing relies on a guide RNA that binds to a desired DNA sequence and a Cas9 enzyme that cuts both strands of DNA at that site, creating a double-strand break. Scientists edit the sequences at the cut ends before using different approaches to guide repair. However, there are often additional DNA sequences with blunt ends in the nucleus that could accidentally get jumbled with the cut ends during repair, leading to mutations. Therefore, researchers adapted CRISPR-Cas9 techniques...