“Wow! Badass. 13,200 crispr base edits in a single cell! On the way to ‘recoded’ human cells,” tweeted Antonio Regalado before covering the news in MIT Technology Review. To be honest, the radical redesign of species is still sci-fi dystopia, but the paper preprinted by Cory J. Smith et al. in bioRxiv is impressive anyway.
By using a set of CRISPR base-editors they mutated thousands of loci per cell, improving the actual capabilities by several orders of magnitude without triggering DNA damage. The experiment targeted repetitive elements called LINE-1 and the same approach could be used to disrupt other high copies sequences suspected of having roles in human diseases. Large-scale editing is therefore opening new opportunities to study the ‘dark matter’ of the genome by probing at the functions of transposable elements.
“For instance, large-scale inactivation of HERV-W and LINE-1 elements could help investigate their respective roles in multiple sclerosis and neurological processes” the authors write. And if this is not enough, “combinatorial functional genomic assays would enable the study of complex genetic traits with applications in evolutionary biology, population genetics, and human disease pathology.”
Multiplex editing has already permitted the development of successfully engineered cell treatments, such as the CAR therapies, which require the simultaneous editing of three target genes. “Future treatments may require many more modifications to augment cancer immunotherapies, slow down oncogenic growth, and reduce adverse effects, such as host-versus-graft disease.”