DNA Base Editing Strategies for Genome Editing

The choice of base editing technology is critical for the success of a gene editing experiment but can seem overwhelming, as each component of the base editing machinery has been altered and refined in the last four years since the first description of base editors for gene editing in 2016. For example, deaminase domains have been changed, base editor architectures and linkers shuffled, different Cas9 variants swapped in, and components subjected to structure-guided mutagenesis, codon optimization, and directed evolution. Below, we outline the base editing tools available and discuss their relative merits, limitations, and suitability for different applications in drug discovery, functional genomics, and therapeutic genome editing. We focus on three main principles: efficiency, precision, and specificity.