Pew Charitable Trust Award

The Sternberg lab will discover and develop new CRISPR–Cas systems with enhanced efficiency and safety. CRISPR is a powerful genome editing tool that can be directed to cut and permanently modify a specific target gene. To accomplish this, most versions of CRISPR first break the DNA backbone, an event that can trigger adverse cellular side effects such as large genome deletions. Recently, I discovered that certain 'jumping genes'— mobile genetic elements found in all domains of life, including bacteria and humans—employ variant CRISPR systems to move themselves from one chromosomal site to another, without making DNA breaks. Now, my lab will dissect the molecular mechanisms of this pathway and leverage these CRISPR systems as a new gene knock-in tool, with fewer negative consequences for the cell. Notably, we will use the system to inactivate antibiotic resistance genes in multidrug-resistant bacteria and to deliver therapeutic genes into human cells. Our work will enhance the precision of genetic engineering and advance a technology that may be safer for use in clinical settings.