Evidence map›Paper›PMID 40763014›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Engineered Un1Cas12f1 with boosted gene-editing activity and expanded genomic coverage.

Li Chen, Xujiao Zhou, Chengsi Huang, Yirou Zhang, Changchang Xin, Jiaxu Hong, Yu Wang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
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

7 authors.

Li Chen *College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China.ORCID 0000-0001-8978-0864
Xujiao Zhou *Department of Ophthalmology, Shanghai Eye, Ear, Nose and Throat Hospital, State Key Laboratory of Brain Function and Disorders, Fudan University, Shanghai 200031, China.
Chengsi HuangCollege of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China.
Yirou ZhangDepartment of Ophthalmology, Shanghai Eye, Ear, Nose and Throat Hospital, State Key Laboratory of Brain Function and Disorders, Fudan University, Shanghai 200031, China.
Changchang XinDepartment of Ophthalmology, Shanghai Eye, Ear, Nose and Throat Hospital, State Key Laboratory of Brain Function and Disorders, Fudan University, Shanghai 200031, China.
Jiaxu HongDepartment of Ophthalmology, Shanghai Eye, Ear, Nose and Throat Hospital, State Key Laboratory of Brain Function and Disorders, Fudan University, Shanghai 200031, China.
Yu WangCollege of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China.ORCID 0000-0002-5188-4622

Funding

Department of Science and Technology of Guangdong Province 2021QN020576MOST | NSFC | National Science Fund for Distinguished Young Scholars (NSF for Distinguished Young Scholars) 82425015National Natural Science Foundation of China 82171102National Natural Science Foundation of China 82273967National Natural Science Fundation of China 82271044National Youth talent support program QWF158001Nation Key Research and Development Program of China 2023YFA0915000Shanghai Medical Innovation Research Program 22Y21900900Shanghai Municipal Commission of Health 20254Z0019Shanghai Science and Technology Innovation Action Plan for Advanced Materials 24CL2900802Shanghai Science and Technology Innovation Action Plan for Cell and Gene Therapy 24J22800500(the "Dawn" Program of) Shanghai Municipal Education Commission 24SG11
6 · The paper itself

Abstract

Compact programmable nucleases provide versatile genome editing tools with therapeutic potential, particularly when delivered via adeno-associated virus (AAV) vectors. However, their limited editing efficacy and stringent protospaceradjacent motif (PAM) requirements impose significant limitations in practical application. Here, we engineered MiniCasUltra, an optimized Un1Cas12f1 variant, through rational mutagenesis. MiniCasUltra exhibits sixfold higher editing activity than Un1Cas12f1, minimal off-target effects (on/off-target ratio > 10), and an expanded PAM preference (5'-WBTR). Using a single AAV vector encoding MiniCasUltra and two single-guide RNAs, we achieved simultaneous editing of two disease-causing genes (

Indexed as

Gene EditingAnimalsCRISPR-Cas SystemsDependovirusGenetic TherapyGenetic VectorsHEK293 CellsHumansMicePTEN PhosphohydrolaseRNA, Guide, CRISPR-Cas SystemsPTEN PhosphohydrolaseRNA, Guide, CRISPR-Cas Systemscompact programmable nucleasesgenome editingMiniCasUltraneovascular age-related macular degenerationUn1Cas12f1

Identifiers

PMID40763014
PMCPMC12358892

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Registered trials

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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.