Harnessing CRISPR-Cas system diversity for gene editing technologies

Abstract

The discovery and utilization of RNA-guided surveillance complexes, such as CRISPR-Cas9, for sequence-specific DNA or RNA cleavage, has revolutionised the process of gene modification or knockdown. To optimise the use of this technology, an exploratory race has ensued to discover or develop new RNA-guided endonucleases with the most flexible sequence targeting requirements, coupled with high cleavage efficacy and specificity. Here we review the constraints of existing gene editing and assess the merits of exploiting the diversity of CRISPR-Cas effectors as a methodology for surmounting these limitations.

Immunogenicity of CRISPR therapeutics—Critical considerations for clinical translation

“…CRISPR-Cas systems are present in about 50% of bacteria and 90% of archaea ( Hille et al, 2018 ; Arroyo-Olarte et al, 2021 ). As an adaptive immune system that provides a survival advantage, an expansive number of diverse CRISPR systems and associated proteins have evolved ( Makarova et al, 2020 ; McKay and Burgio, 2021 ). Early studies have focused on S. pyogenes and S. aureus CRISPR-Cas9 systems, but now other CRISPR systems are being explored for their different efficiencies, specificities, and targeting requirements ( Adli, 2018 ; Batool et al, 2021 ; McKay and Burgio, 2021 ).…”

“…As an adaptive immune system that provides a survival advantage, an expansive number of diverse CRISPR systems and associated proteins have evolved ( Makarova et al, 2020 ; McKay and Burgio, 2021 ). Early studies have focused on S. pyogenes and S. aureus CRISPR-Cas9 systems, but now other CRISPR systems are being explored for their different efficiencies, specificities, and targeting requirements ( Adli, 2018 ; Batool et al, 2021 ; McKay and Burgio, 2021 ). This diversity may provide an opportunity to avoid pre-existing immunity by using CRISPR effectors from less ubiquitous prokaryotes such as extremophiles.…”