Abstract
DNA can be engineered to produce new biologics, gene therapies, and cellular therapies, and to reprogram organisms. Having the ability to engineer DNA at scale can accelerate the development of these applications. Existing technologies excel at short oligonucleotide synthesis by chemical or enzymatic methods (up to 2000 bp) and intermediate-size DNA assembly (up to 5-7 kb). Yet synthesizing sequence-validated longer DNA (>10 kb) and/or constructing highly complex combinatorial DNA libraries at scale remains a significant challenge, due largely to technical and cost barriers. Inspired by recent studies on an in vivo DNA processing platform for megabase-long DNA assembly and on high-throughput sequence verification, we discuss how these platforms may be used to achieve DNA engineering at scale.