Scientific Advances: Potential novel gene therapy opportunities revealed by CRISPR CopyCatchers

Gene conversion events represent the exchange of genomic information from one chromosome to its homolog. Based on the effectiveness of CRISPR gene-drive technologies, the lab of Ethan Bier recently published a study in which they visualize gene conversion (GC) events between homologous chromosomes. Exchange of DNA via homology directed repair is thought to be a relatively rare event. However, after CRISPR-induced double strand break formation the authors report GC frequencies between 0-50% in various fruitfly tissues using the CopyCatcher fluorescent reporter construct at two different loci. In human 293 HEK cells CRISPR-induced breaks resulted in GC events in 4-8% of the cells as indicated by the CopyCatcher reporter. Notably, high c-MYC expression correlated with reduced CG activity. The authors propose the CRISPR-induced somatic gene conversion events may proof a valid therapeutic route to establish functional alleles in patients with two distinct mutant alleles. Indeed, natural gene correction events through GC have been reported in literature previously.

For more information, see: Li, Z., et al. (2021) CopyCatchers are versatile active genetic elements that detect and quantify inter-homolog somatic gene conversion, Nat. Comm.

Keywords: CRISPR, gene conversion, fluorescent reporter

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