UC San Diego

Base editors are a new family of programmable genome editing tools capable of introducing highly efficient single base changes. These fusion enzymes take advantage of CRISPR-Cas gRNA technology to access genomic targets of interest but use tethered single stranded DNA modifying enzymes to directly chemically modify DNA. While base editors are highly modular and have been tailored to tackle a wide array of targets, to date these tools have been restricted to limited types of chemical modifications and there remains a subset of base conversions that cannot be achieved with great precision. Base editors that utilize new chemistries could theoretically fill this need. Here, I present an argument for utilizing guanine deamination chemistry towards development of a novel G·C to A·T editor. Engineering of an enzyme capable of facilitating this change would benefit from further characterization of the development process of currently available base editors. To this end, I present a systematic reversion analysis study of the first fully engineered adenine base editor ABE7.10, along with the discovery of additional functionality afforded by a new class of Minimally Evolved Adenine Base Editors (ME-ABEs). Finally, given the ever-growing use of these tools and their intersection with multiple scientific domains, the need for accessible curricula to excite and train the next generation of scientists is clear. To address this, I present the Genome Engineering Technologies Research-Practice Partnership, a collaboration between university researchers and high school students that brings base editing to the classroom.