A new version of the CRISPR-Cas9 protein has been developed that can increase the targeting efficiency of the gene editing process.

Currently the CRISPR Cas-9 system is the most widely used gene editing technique. However, concerns about CRISPR editing genes other than the ones it is targeted to have hindered its introduction into gene-therapy treatments for patients. It is possible that these ‘off target mutations’, as they are known, could cause detrimental gene edits that lead to cancer or other diseases.

Cas9 is the protein component of the CRISPR system, that searches through the genome to find the target DNA to edit. Cas9 must be able to do this precisely to avoid making cuts at other parts of the genome. One of the commonly used variations of Cas9 is SpCas9, meaning the Cas9 enzyme sourced from the bacteria Streptococcus pyogenes.

Variations of Cas9 have already been engineered to try and improve its specificity. However, these variations are still too big to comfortably fit inside the viral delivery vectors used to deliver the CRISPR vectors into cells for gene therapy. Developing a smaller and specific version of Cas9 would drive the incorporation of CRISPR gene therapies into the clinic.

The newly engineered SaCas9-HF enzyme was found to reduce off-target activity by 90%, compared to the wild type enzyme. It is also small enough to fit comfortably within the viral delivery vectors. The new Cas9 variant may therefore hold promise for increasing the efficacy of gene therapies.