A Dual-Deaminase CRISPR Base Editor Enables Concurrent Adenine and Cytosine Editing

Adenine and cytosine base editors enable programmable modification of A-to-G and C-to-T DNA edits, respectively. However, existing editors can induce only a single type of modification, thereby limiting the range of DNA alterations that can be created. Here we describe a CRISPR-Cas9-based Synchronous Programmable Adenine and Cytosine Editor (SPACE) fusion that can concurrently introduce A-to-G and C-to-T substitutions with minimal numbers of RNA off-target edits. SPACE enables the creation of an expanded range of diverse DNA sequence alterations, codon changes, and amino acid substitutions, thereby further broadening the research applications of CRISPR base editors.