Atlas of CRISPR Correction of Pathogenic Variants

This document is a research article that presents the mEdit platform, which evaluates the therapeutic editability of pathogenic and likely pathogenic human genetic variants using CRISPR technology. The study identifies a library of 179,819 variants across 4,659 genes, detailing their potential for correction through CRISPR-based approaches. The mEdit platform assesses these variants by providing mutation-specific guide RNAs (gRNAs), efficiency scores, off-target evaluations, and variant annotations. The findings indicate that over 95% of the variants are targetable by at least one CRISPR tool, with more than 14% suitable for base editing strategies. Additionally, the article introduces the concept of histoetiology, which assigns root-cause tissues to these variants, enhancing the understanding of their clinical editing tractability. The research establishes a strategic roadmap for prioritizing CRISPR-based therapeutic development, highlighting the potential of CRISPR technologies to address numerous genetic disorders and nominating approximately 25% of the human mutome as amenable to clinical CRISPR gene editing.