Pre-symptomatic gene editing for hypertrophic cardiomyopathy: In our latest News & Views, Alanna Strong discusses new preclinical data and concludes that, despite the challenges, it is a strategy worth pursuing in the clinic. ChildrensPhila PennMedicine
The two groups use distinct but complementary approaches involving CRISPR–Cas9 adenine base editing to target a well-studied missense variant in thegene . This pathogenic variant increases sarcomere contractility via a dominant-negative mechanism; genetic treatment therefore requires allele correction or deletion.
Although ABE can achieve highly efficient and precise correction, it is limited to scenarios where editing adenine to guanine reverts the gene to wild-type function, and where the target adenine lies within a ‘window’ at a defined distance upstream of the protospacer adjacent motif used by the base editor to engage the genomic site.
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