Cas12 and TnpB Variants: Expanding the CRISPR Toolkit for Editing and Diagnostics
This Nature Biotechnology review comprehensively compares the molecular features of natural and engineered Cas12 and ancestral TnpB variants, which have independently evolved multiple times from transposon-associated ancestors. The authors catalogue the remarkable diversity in size, guide structure, and interference strategy across the Cas12 family and survey their established applications in genome editing and CRISPR-based diagnostics. For clinical laboratories, Cas12-based platforms like DETECTR are particularly relevant as emerging rapid molecular diagnostic tools.
The original study
Biology and applications of CRISPR-Cas12 and transposon-associated homologs.
- Authors
- Wu WY, Adiego-Pérez B, van der Oost J
- Journal
- Nature biotechnology
- Type
- Journal Article, Review
- PMID
- 39633151
Original abstract
CRISPR-associated Cas12 proteins are a highly variable collection of nucleic acid-targeting proteins. All Cas12 variants use RNA guides and a single nuclease domain to target complementary DNA or, in rare cases, RNA. The high variability of Cas12 effectors can be explained by a series of independent evolution events from different transposon-associated TnpB-like ancestors. Despite basic structural and functional similarities, this has resulted in unprecedented variation of the Cas12 effector proteins in terms of size, domain composition, guide structure, target identity and interference strategy. In this Review, we compare the unique molecular features of natural and engineered Cas12 and TnpB variants. Furthermore, we provide an overview of established genome editing and diagnostic applications and discuss potential future directions.