High-fidelity Cas9 provides highly efficient genome editing with reduced off-target effects in primary cells
Vakulskas C, Dever D, et al. (2018) A novel high-fidelity Cas9 delivered as a ribonucleoprotein complex enables high frequency gene editing in human haematopoietic stem and progenitor cells. Nature Medicine, DOI 10.1038/s41591-018-0137-0 .
Ex vivo RNP-mediated Cas9 genome editing of human hematopoietic stem and progenitor cells (HSPCs) will likely be one of the first Cas9 editing programs to enter clinical phases. Recent studies have shown that disease-causing mutations can be corrected using CRISPR-Cas9 in long-term engrafting HSPCs that are preserved in downstream lineages [2–5]. However, an on-going concern for many researchers is off-target activity introduced by the CRISPR/Cas9 system, which could lead to loss of some critical stem cell functions, or worse, the creation of cancer-causing mutations .