Caltech's ACE method moves 2M bases of DNA in one step, creating cross-genus bacterial chimeras

NikoMcCarty · x · 2026-11-11

A new paper from Kaihang Wang's group at Caltech describes ACE (Additive Conjugative-CAST Engineering), which transfers 2 million bases of DNA between bacteria in a single step, creating chimeras carrying 4.6M bases from E. coli DH10B, 2M from recoded Syn61, and 900kb from Shigella — working across bacterial genera.

How it works: target DNA is flanked with CassetteSTART/END sequences; a helper plasmid moves it via conjugation; a second helper plasmid integrates it at a chosen locus via a CRISPR-associated transposase.

Results: 1,000 successful colonies per experiment for a 1M-base strand; 98.1–99.7% of insertions landed at intended sites across three targets; RNA-seq confirmed all donor genes were expressed.

Why it matters: a cheaper, scalable way to port biosynthetic pathways into strains suited for biomanufacturing, and it works with synthetic DNA — a strain could serve as a perpetual donor. The project has been running for at least 8 years.

Related event: Caltech's ACE Method Moves 2 Million Base Pairs in One Step to Build Chimeric Genomes(2 posts)→

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