Delivering the promise of CRISPR-Cas precision medicine

Widespread adoption of CRISPR-Cas methods has sparked a revolution in genome engineering and precision medicine. Scientists are now able to insert, delete, rewrite, and regulate specific gene sequences, both in vitro and in vivo.

The major barrier to further progress is the lagging capability to efficiently deliver Cas nucleases and single guide RNAs into cells.

To meet this need, we are collaborating with the Stevens lab, who have developed a nanoparticle delivery system based on a bioreducible polymer.

We found that the reagent outperforms the gold-standard commercial reagents for delivery of CRISPR-Cas ribonucleoproteins (RNPs) in vitro. The system can safely and effectively deliver to a variety of targets also in vivo.

The nanoparticles were also adapted to deliver DNA-free prime-editing RNP payloads, paving the way for clinical translation by minimizing genotoxicity.

By developing this delivery platform for CRISPR-Cas RNPs to maturity, we will 1) eliminate a major barrier to effective genome editing in cultured cells, and 2) enable safe and effective delivery of RNP payloads in vivo.

These results will help deliver the promise of emerging gene editing technologies, both to the scientists who rely on efficient genome engineering in research, and to clinicians who await a means to deliver existing precision therapies to their patients.