Background

One version of the CRISPR/Cas system, CRISPR/Cas12a, has been modified to provide useful tools for editing genomes. Cas12a-type nucleases have gained popularity due to their versatility and simplicity as compared to Cas9. These systems are useful but have some important limitations regarding efficiency and accuracy of targeted editing, resulting in impediments when used for commercially relevant applications. Therefore, a need exists for improved nucleic acid guided nucleases for directed and accurate editing with improved efficiency.

Technology Overview

Researchers from the University of Colorado have developed a method of engineering chimeric Cas12a-type nucleases for improved targeted gene editing. This method was used to create 560 synthetic Cas12a-type nucleases, resulting in nucleases with diverse PAM preferences and on/off-targeting specificity. In addition to advantages afforded by Cas12a (AT rich PAM, staggered cuts, and simpler multiplex editing), these chimeric nucleases have capabilities to fit specific gene editing needs.

Further Details

Liu, R.M., Liang, L.L., Freed, E. et al. Synthetic chimeric nucleases function for efficient genome editing. Nat Commun 10, 5524 (2019). https://doi.org/10.1038/s41467-019-13500-y

Stage of Development

Technology Readiness Level (TRL): 4.

Benefits

Alternative PAM preferences
Higher specificity to wild-type sequences
Activity demonstrated in yeast and HEK293T cells
Multiple nuclease options to suit specific genome editing needs
Methodology can be used to create further tailored nuclease

Chimeric Cas12a-type Nucleases for CRISPR Gene Editing

Patents

IP Status