Physics / mechanism
CRISPR-Cas9 and its successors (Cas12, Cas13, base editors, prime editors) use a guide RNA to direct an endonuclease to a specific genomic locus via Watson-Crick base pairing, inducing a double-strand break or precise base conversion. Editing efficiency in primary human cells now reaches 80–95% with optimised delivery; off-target rates for base editors sit below 0.1% with high-fidelity variants. Prime editing achieves all 12 base-to-base conversions plus small indels without DSBs. Delivery remains the binding constraint: LNP formulations dominate liver targets; AAV capsids are size-limited (~4.7 kb); non-viral approaches (electroporation, VLPs) are expanding the addressable tissue window.
Competitive landscape
Base editing and prime editing compete directly with nuclease-based CRISPR for precision applications. Zinc-finger nucleases (ZFNs) and TALENs predate CRISPR but retain niche use in therapeutic GMP contexts. Epigenome editors (CRISPRa/i) compete for gene-regulation applications without permanent edits. Synthetic biology platforms—site-specific recombinases, transposons (INTEGRATE system)—address large-sequence insertion where prime editing is insufficient.
Companies using
Connected ideas
Sources
Frontier (open questions)
- To be added.