Genome editing technology has been heralded for its ability to revolutionize the healthcare and pharmaceutical industry.
A large question that remains is how to control the gene editing complex and make gene editing safe and implementable for human therapeutics and personalized medicine. Although there have been numerous advances in modifying the CRISPR/Cas system itself for more precise and efficient DNA editing, newly developed anti-CRISPR’s and RNA-targeting CRISPR/Cas systems would expand the toolbox for controlled editing and get us closer to efficacious and safe gene editing.
At Sandia, we are working to develop two modes of safe gene editing:
- Targeted delivery of anti-CRISPR’s to allow for specific, localized, and kinetically controlled CRISPR/Cas editing. In addition to targeted delivery, we are investigating several anti-CRISPR’s with academic partners to create a toolbox with multiple avenues for editing inhibition including both competitive inhibitors that prevent CRISPR/Cas activity and catalytically active anti-CRISPR’s that inactivate the CRISPR/Cas complex.
- CRISPR/Cas systems engineered for RNA-targeting, rather than DNA gene editing, for temporary and controllable changes to gene expression. Importantly, Cas9 from Staphylococcus aureus(SauCas9) RNA-scission depends only on an sgRNA and does not need a PAMmer, thereby simplifying outstanding issues in delivery. With its small size, SauCas9 could easily be implemented for RNA-targeting applications.
Combined, our anti-CRISPR and RNA-targeting approaches have the potential to make human gene editing therapies safer and more controllable. These advancements propel CRISPR/Cas strategies forward towards realizing their impact on human health and will provide a larger design space for therapeutic intervention.