Paper of the field n°5
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Abstract for General public
Variations within the human genome affect the safety of genome-editing treatment in different patients.
Genome-editing treatments may produce unintended edits in the genome, known as “off-target” effects. Before any CRISPR treatment can be used in clinical trials, it’s crucial to carefully test for potentially harmful off-target events. The human genome consists of numerous single nucleotide variants (SNVs), small changes that make the genome sequence of every individual slightly different. However, most studies that address the off-target safety issue, rely on a representative single “reference genome”. In this paper, the researchers demonstrated the importance of considering a diverse range of genomes from various ethnic backgrounds. They used a computational tool that forecasts potential off-target sites using a haplotype-aware database, that integrates SNV information, as well as other details, such as sex and age. The researchers found that the guide RNA used in CASEGVY, the currently approved sickle-cell disease CRISPR treatment, has an off-target site specifically in people of African ancestry, which previous studies relying solely on the reference genome completely missed. This finding emphasizes the need for a personalized approach in developing new genome-editing treatments, taking into account the genetic diversity of all individuals.
Abstract written by Nechama Kalter from Bar Ilan University (Israel)
Cancellieri, Samuele, et al. « Human Genetic Diversity Alters Off-Target Outcomes of Therapeutic Gene Editing ». Nature Genetics, vol. 55, no 1, janvier 2023, p. 34‑43. https://doi.org/10.1038/s41588-022-01257-y.
