Evidence map›Paper›PMID 41554741›Full record

ArticleNature communications2026

Engineering the MmeFz2-ωRNA system for efficient genome editing through an integrated computational-experimental framework.

Shangpu Li, Kun Xu, Guoling Li, Henan Jiang, Zhenmin Wu, Pengfei Gao, Yang Yue, Yufei Chen, Zujiang Liu, Bingqian Zhou and 6 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Shangpu Li *International Joint Agriculture Research Center for Animal Bio-Breeding of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
Kun Xu *International Joint Agriculture Research Center for Animal Bio-Breeding of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.ORCID 0000-0001-5714-9090
Guoling Li *Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, Guangdong, China.ORCID 0000-0003-0422-6157
Henan Jiang *International Joint Agriculture Research Center for Animal Bio-Breeding of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
Zhenmin Wu *International Joint Agriculture Research Center for Animal Bio-Breeding of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
Pengfei Gao *International Joint Agriculture Research Center for Animal Bio-Breeding of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
Yang YueInternational Joint Agriculture Research Center for Animal Bio-Breeding of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
Yufei ChenInternational Joint Agriculture Research Center for Animal Bio-Breeding of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
Zujiang LiuInternational Joint Agriculture Research Center for Animal Bio-Breeding of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
Bingqian ZhouInternational Joint Agriculture Research Center for Animal Bio-Breeding of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
Min ZhouLife Science Research Core Services, Northwest A&F University, Yangling, Shaanxi, China.
Yulin ChenInternational Joint Agriculture Research Center for Animal Bio-Breeding of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.ORCID 0000-0001-5679-4055
Xu LiuKey Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China. liuxu1658@nwafu.edu.cn.
Xiaolong WangInternational Joint Agriculture Research Center for Animal Bio-Breeding of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China. xiaolongwang@nwafu.edu.cn.ORCID 0000-0003-1620-1344
Zhaowei WuSchool of Physical Science and Technology, ShanghaiTech University, Shanghai, China. wuzw1@shanghaitech.edu.cn.ORCID 0000-0001-8952-0181
Yinghui WeiInternational Joint Agriculture Research Center for Animal Bio-Breeding of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China. yinghuiwei@nwafu.edu.cn.ORCID 0000-0002-6642-1559

Funding

China Agricultural Research SystemNational Natural Science Foundation of China (National Science Foundation of China) 22207074National Natural Science Foundation of China (National Science Foundation of China) 32441080, 32301251
6 · The paper itself

Abstract

Eukaryotic Fanzor proteins are compact, programmable RNA-guided nucleases with substantial potential for genome editing, although their efficiency in mammalian cells remains suboptimal. Here, we present a combinatorial engineering strategy to optimize a representative Fanzor system, MmeFz2-ωRNA. AlphaFold3-powered rational redesign produced a minimized ωRNA scaffold that is 30% smaller while maintaining up to 82.2% efficiency. Synergistic structure-guided and AI-augmented protein engineering generated two variants, enMmeFz2 and evoMmeFz2, which exhibited an average ~32-fold increase in activity across 38 genomic loci. Moreover, fusion of the non-specific DNA-binding domain HMG-D further enhanced editing performance (enMmeFz2-HMG-D and evoMmeFz2-HMG-D). Notably, evoMmeFz2-HMG-D demonstrated robust in vivo genome editing activity, enabling dystrophin restoration in humanized male Duchenne muscular dystrophy mouse models via single adeno-associated virus (AAV) delivery. This study establishes Fanzor2 as a gene editing platform for genome engineering and therapeutic applications, and underscores the power of AI-guided engineering to accelerate genome editor development while reducing experimental burden.

Indexed as

RNAAnimalsDependovirusDystrophinGenetic EngineeringHEK293 CellsHumansMaleMiceMuscular Dystrophy, DuchenneProtein EngineeringDystrophinRNA

Identifiers

PMID41554741
PMCPMC12923547

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.