CRISPR-Cas9-Mediated Mutagenesis: Mind the Gap?

Lydia Teboul,Andy Greenfield

doi:10.1089/crispr.2018.29027.gre

Lydia Teboul, Andy Greenfield

Open Access

https://doi.org/10.1089/crispr.2018.29027.gre

Copy DOI

Abstract

CRISPR-Cas9-Mediated Mutagenesis: Mind the Gap?

Highlights

The most recent challenge to CRISPR-Cas[9] gene editing technology comes from Kosicki et al in Nature Biotechnology[2] entitled ‘‘Repair of CRISPR-Cas9-induced double-stranded breaks leads to large deletions and complex rearrangements.’’ This study, from Allan Bradley’s group at the Wellcome Sanger Institute, is different because it relies on a robust methodology
‘‘Pathogenic Consequences’’? According to Kosicki et al, these observations may toll the bell for CRISPR-Cas[9] as a therapeutic tool: ‘‘The observed genomic damage in mitotically active cells caused by CRISPR–Cas[9] editing may have pathogenic consequences.’’ They contend that induced translocations, deletions, or inversions may have longrange effects, altering adjacent loci, possibly leading to a carcinogenic ‘‘hit’’ in stem cells and progenitors, which might become neoplastic over time
In some proposed clinical contexts, selection will not be possible. This may result in greater exploration of genome editing methodologies that do not employ DNA cutting, such as base editing.[7]

Summary

Introduction

Genome Editing and Human Reproduction: Social and Ethical Issues. A New Study Documenting CRISPR-Induced On-Target Large(r) Deletions and Rearrangements Highlights the Risks Associated with Such Events CRISPR*-Cas[9] genome editing has created much excitement and no small amount of controversy.

Results

Conclusion