Architecture of a DNA-guided Cas12a

bioRxiv (Cold Spring Harbor Laboratory) 2026 Preprint Open access

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Authors: Rodrigo Fregoso Ocampo, Carlos Orosco, Boyu Huang, M. Stewart West, Piyush Kumar Jain, David Ward Taylor
DOI: 10.64898/2026.03.19.712971
Cited by: 1
References: 20

Abstract

Abstract CRISPR/Cas systems have largely been restricted to RNA-guided nucleases. Here, we present the cryo-EM structure of Acidaminococcus sp. Cas12a (AsCas12a) bound to a pseudo-DNA (ΨDNA) guide and RNA target, revealing how Cas12a accomplishes DNA-guided RNA recognition. The ΨDNA hairpin bridges the recognition and nuclease lobes, mimicking a PAM-proximal duplex and positioning the spacer to allow formation of a canonical RNA-DNA heteroduplex along the REC lobe. This provides a structural framework for its activity and provides a blueprint for future engineering.

Fields of Study & Subjects

CRISPR and Genetic Engineering Advanced biosensing and bioanalysis techniques RNA and protein synthesis mechanisms

Publication details

Journal / source
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Publication date
20 March 2026
Language
EN
Document type
Preprint