New CRISPR, New Function with Leo Vo

Episode Summary:

In a single decade, CRISPR has made a dramatic impact on literally every facet of biotechnology. This game-changing system is traditionally programmed to make cuts at very specific parts of the genome, altering the code to cure disease. But a new class of CRISPRs discovered by Leo’s colleagues don’t simply cut DNA -- they integrate entirely new genetic material at targeted locations. With it, Leo generates a new method to perform very specific and highly efficient genome engineering on bacteria and describes the multitude of ways it can generate strains that revolutize commodity molecule synthesis and medicine.

Episode Notes:

About the Author

Leo is a PhD candidate who performed this work under Professor Sam Sternberg at Columbia University in New York City. Dr. Sternburg and his team are world experts in CRISPR biology having discovered multiple new CRISPR systems, including the function of Cas9 during his time in Professor Jennifer Doudna’s lab.Leo was driven to become a synthetic biologist after being exposed to all the ways nature has engineered biology to overcome problems. 

Key Takeaways

A new class of CRISPRs have been discovered that don't cut DNA but instead integrate new DNA on the genome.Leo hijacks this CRISPR’s novel functionality to integrate whatever new DNA he wants into whatever location on a genome he desires. Through the tools of synthetic biology, the system generates extremely targeted integrations at high efficiency in bacterial cells.This CRISPR tool allows for integration of huge genetic payloads, iterative integrations, and integration of payloads at multiple locations in a single step, all of which create entirely new options for strain engineering.The tool can be applied to multiple bacterial species and has proven utility in engineering the microbiome in situ as well as modifying industrially sought after strains. 

Translation

Leo demonstrates that the system is highly effective in laboratory settings and can be optimized to overcome new challenges in new bacterial hosts.The tool is undergoing further development and optimization to do population scale engineering -- making targeted and useful modifications to bacteria in communities like those seen in our gut or in nature. Further research is needed to move this powerful integration tool into human cells as a novel method to overcome genetic disease and engineer future cell therapies.

First Author: Leo Vo

Paper: 

CRISPR RNA-guided integrases for high-efficiency, multiplexed bacterial genome engineering, Nature Biotechnology, 2020.