Base Editing: Genome Editing Without Double-Stranded DNA Cleavage

Abstract
In this lecture I will describe the development, early application, and expansion of base editing, a new approach to genome editing that enables programmable correction of point mutations efficiently without requiring DNA backbone cleavage or donor DNA templates. Base editing has the potential to advance the scope and effectiveness of genome editing of point mutations, which represent the substantial majority of known human genetic variants associated with disease but are difficult to correct cleanly and efficiently using standard genome editing methods. Recent developments have enhanced the efficiency, product purity, targeting scope, precision, and conversion capabilities of base editing, increasing its potential to study and treat human genetic diseases.

 

Biosketch
Nicole Gaudelli receieved her B.S. degree in biochemistry from Boston College in May of 2006. While at Boston College she conducted research under the guidance of Professor Steve Bruner to elucidate the enzymatic mechanisms of an aminotransferase involved in neocrazinostatin biosynthesis and a non-heme iron oxygenase involved in vancomycin assembly. She then joined the laboratory of Professor Craig Townsend at Johns Hopkins University where she studied a non-ribosmal peptide synthetase (NRPS) implicated in the biosynthesis of the β-lactam antibiotic nocardicin. In her doctoral work she elucidated the mechanism through which monobactam anitbiotics are biosynthesized. She next pursued postdoctoral work in the laboratory of Professor David R. Liu where she expanded the capabilities of the base-editing technology by creating an adenine base editor (ABE), through 7 rounds of evolution and engineering, which cleanly converts A•T base pairs to G•C base pairs in a programmable manner, with low indel %, and without double-stranded DNA breaks.