Engineered circular guide RNAs enhance miniature CRISPR/Cas12f-based gene activation and adenine base editing

Xin Zhang, Mengrao Li, Kechen Chen, Yuchen Liu, Jiawei Liu, Jiahong Wang, Hongxin Huang, Yanqun Zhang, Tao Huang, Shufeng Ma, Kaitong Liao, Jiayi Zhou, Mei Wang, Ying Lin () and Zhili Rong ()
Additional contact information
Xin Zhang: Southern Medical University
Mengrao Li: Southern Medical University
Kechen Chen: Southern Medical University
Yuchen Liu: Southern Medical University
Jiawei Liu: Southern Medical University
Jiahong Wang: Southern Medical University
Hongxin Huang: Southern Medical University
Yanqun Zhang: Southern Medical University
Tao Huang: Southern Medical University
Shufeng Ma: Southern Medical University
Kaitong Liao: Southern Medical University
Jiayi Zhou: Southern Medical University
Mei Wang: Southern Medical University
Ying Lin: Southern Medical University
Zhili Rong: Southern Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-9

Abstract: Abstract CRISPR system has been widely used due to its precision and versatility in gene editing. Un1Cas12f1 from uncultured archaeon (hereafter referred to as Cas12f), known for its compact size (529 aa), exhibits obvious delivery advantage for gene editing in vitro and in vivo. However, its activity remains suboptimal. In this study, we engineer circular guide RNA (cgRNA) for Cas12f and significantly improve the efficiency of gene activation about 1.9–19.2-fold. When combined with a phase separation system, the activation efficiency is further increased about 2.3–3.9-fold. In addition, cgRNA enhances the editing efficiency and narrows the editing window of adenine base editing about 1.2–2.5-fold. Importantly, this optimization strategy also boosts the Cas12f-induced gene activation efficiency in mouse liver. Therefore, we demonstrate that cgRNA is able to enhance Cas12f-based gene activation and adenine base editing, which holds great potential for gene therapy.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-58367-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58367-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-58367-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().