Evidence map›Paper›PMID 42052652›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Design of Safe and Efficient Adenine Base Editors via Protein Language Model Screening for Osteoarthritis Treatment.

Jiawei Yao, Dalin Chen, Ziyi Zhang, Jingxuan Ren, Chengcheng Zhao, Shengfang Wang, Mengyu Shang, Dawei Jiang, Yinuo Li, Su'an Tang and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Jiawei YaoGuangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
Dalin ChenGuangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.ORCID https://orcid.org/0009-0004-1947-7463
Ziyi ZhangState Key Laboratory of Common Mechanism Research for Major Diseases, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, China.
Jingxuan RenState Key Laboratory of Common Mechanism Research for Major Diseases, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, China.
Chengcheng ZhaoGuangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
Shengfang WangGuangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
Mengyu ShangState Key Laboratory of Common Mechanism Research for Major Diseases, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, China.
Dawei JiangGuangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
Yinuo LiState Key Laboratory of Common Mechanism Research for Major Diseases, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, China.
Su'an TangDepartment of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Kai LiGuangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
Xiaohui ZhangState Key Laboratory of Common Mechanism Research for Major Diseases, Suzhou Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, China.
Xiaogang WangGuangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.ORCID https://orcid.org/0000-0001-9798-834X

Funding

CAMS Innovation Fund for Medical Sciences 2025-I2M-QN-008CAMS Innovation Fund for Medical Sciences 2025-I2M-XHXX-173National Natural Science Foundation of China 82350003National Natural Science Foundation of China 82522046
6 · The paper itself

Abstract

Base editors enable precise genome modification and have emerged as a promising therapeutic approach for correcting diseases caused by single-nucleotide variants. While the current efficient version of adenine base editors (ABEs), such as ABE8e, exhibits exceptional efficiency for A-to-G conversions, their clinical translation is hindered by persistent high off-target editing effects. Here, we applied artificial intelligence-assisted design a safe ABE variant, RDLot-ABE, with a narrow(4 nt) editing window and substantially lower DNA off-target editing activity compared to ABE8e. Moreover, targeted knockdown of Fscn1 for osteoarthritis treatment using RDLot-ABE alleviates cartilage degradation in explants derived from human patients. Notably, intra-articular delivery of the RDLot-ABE to reduce Fscn1 effectively arrests disease progression in a murine osteoarthritis model. These findings establish RDLot-ABE as a safe and precise tool, expanding the clinical potential of gene editing therapies.

Indexed as

AdenineGene EditingOsteoarthritisAnimalsDisease Models, AnimalHumansMiceAdeninebase editorminimal off‐targetprotein language modelrational design

Identifiers

PMID42052652
PMCPMC13248760

What OpenQuestion holds

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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.