Evidence map›Paper›PMID 41944347›Full record

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

Cryo-EM Structure Guided Engineering of Botulinum Neurotoxin A With Advanced Receptor Binding Affinity and Therapeutical Benefits.

Wenrui Wang, Zhaxi Zerang, Linjin You, Ziye Liu, Rong Nie, Fuwei Qi, Fenfen Gao, Chengmu Zhao, Wantong Ma, Jinghan He and 7 more

Abstract read
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. 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

17 authors.

Wenrui WangSchool of Pharmacy, Joint Drug Development and Innovation Centre For Neurological Disorders of Lanzhou University-China National Biotec Group-Lanzhou Biotechnology Development Co., Lanzhou University, Lanzhou, Gansu, P. R. China.ORCID https://orcid.org/0009-0008-1442-0459
Zhaxi ZerangMOE Frontiers Science Center for Rare Isotopes, Lanzhou University, Lanzhou, Gansu, P. R. China.
Linjin YouSchool of Pharmacy, Joint Drug Development and Innovation Centre For Neurological Disorders of Lanzhou University-China National Biotec Group-Lanzhou Biotechnology Development Co., Lanzhou University, Lanzhou, Gansu, P. R. China.
Ziye LiuSchool of Pharmacy, Joint Drug Development and Innovation Centre For Neurological Disorders of Lanzhou University-China National Biotec Group-Lanzhou Biotechnology Development Co., Lanzhou University, Lanzhou, Gansu, P. R. China.
Rong NieSchool of Pharmacy, Joint Drug Development and Innovation Centre For Neurological Disorders of Lanzhou University-China National Biotec Group-Lanzhou Biotechnology Development Co., Lanzhou University, Lanzhou, Gansu, P. R. China.
Fuwei QiSchool of Pharmacy, Joint Drug Development and Innovation Centre For Neurological Disorders of Lanzhou University-China National Biotec Group-Lanzhou Biotechnology Development Co., Lanzhou University, Lanzhou, Gansu, P. R. China.
Fenfen GaoSchool of Pharmacy, Joint Drug Development and Innovation Centre For Neurological Disorders of Lanzhou University-China National Biotec Group-Lanzhou Biotechnology Development Co., Lanzhou University, Lanzhou, Gansu, P. R. China.
Chengmu ZhaoSchool of Pharmacy, Joint Drug Development and Innovation Centre For Neurological Disorders of Lanzhou University-China National Biotec Group-Lanzhou Biotechnology Development Co., Lanzhou University, Lanzhou, Gansu, P. R. China.
Wantong MaSchool of Pharmacy, Joint Drug Development and Innovation Centre For Neurological Disorders of Lanzhou University-China National Biotec Group-Lanzhou Biotechnology Development Co., Lanzhou University, Lanzhou, Gansu, P. R. China.
Jinghan HeSchool of Pharmacy, Joint Drug Development and Innovation Centre For Neurological Disorders of Lanzhou University-China National Biotec Group-Lanzhou Biotechnology Development Co., Lanzhou University, Lanzhou, Gansu, P. R. China.
Xiaoru WangSchool of Pharmacy, Joint Drug Development and Innovation Centre For Neurological Disorders of Lanzhou University-China National Biotec Group-Lanzhou Biotechnology Development Co., Lanzhou University, Lanzhou, Gansu, P. R. China.
Shanquan WuMOE Frontiers Science Center for Rare Isotopes, Lanzhou University, Lanzhou, Gansu, P. R. China.
Bo LiuSchool of Pharmacy, Joint Drug Development and Innovation Centre For Neurological Disorders of Lanzhou University-China National Biotec Group-Lanzhou Biotechnology Development Co., Lanzhou University, Lanzhou, Gansu, P. R. China.
Xinyao LiuMOE Frontiers Science Center for Rare Isotopes, Lanzhou University, Lanzhou, Gansu, P. R. China.
Dongsheng LeiMOE Frontiers Science Center for Rare Isotopes, Lanzhou University, Lanzhou, Gansu, P. R. China.
Dejuan ZhiSchool of Pharmacy, Joint Drug Development and Innovation Centre For Neurological Disorders of Lanzhou University-China National Biotec Group-Lanzhou Biotechnology Development Co., Lanzhou University, Lanzhou, Gansu, P. R. China.
Dongsheng WangSchool of Pharmacy, Joint Drug Development and Innovation Centre For Neurological Disorders of Lanzhou University-China National Biotec Group-Lanzhou Biotechnology Development Co., Lanzhou University, Lanzhou, Gansu, P. R. China.

Funding

Key Project of Gansu Province Science and Technology, China 22ZD6FA053Lanzhou Chengguan District Science and Technology Bureau Plan Project, Gansu Province, China 2024JSCX0024National Natural Science Foundation of China 32171300National Natural Science Foundation of China 82073825Natural Science Foundation of Gansu Province, China 20JR10RA619
6 · The paper itself

Abstract

Botulinum neurotoxin type A (BoNT/A) has been extensively used in treating a wide range of neurological disorders and aesthetics. However, insufficient binding affinity between BoNT/A and its receptor SV2C could lead to mild to severe side effects. An open active conformation of BoNT/A cryo-EM structure at a resolution of ∼2.85 Å was resolved. Guided by the BoNT/A cryo-EM structure, saturation mutagenesis libraries were constructed and screened by BACTH system to identify mutants that can boost toxin-SV2C affinity. The engineered toxin binding domain achieved up to approximately six-fold improved affinity in SPR analysis, and the engineered toxins exhibited significantly improved binding capacity, and enhanced SNAP25 cleavage efficacy in cultured neurons. Preclinical animal studies, including MLB, DAS, sweat test, and PET/CT assays, demonstrated that the engineered BoNT/A VLTS has higher potency, lower diffusion, and significantly better safety profiles than the BoNT/A wt, which can reduce side effects and benefit future therapeutic applications.

Indexed as

Botulinum Toxins, Type ACryoelectron MicroscopyProtein EngineeringAnimalsHumansProtein BindingBotulinum Toxins, Type Acryo‐EMengineered botulinum toxin Ahigher affinityhigher potencyless toxic

Identifiers

PMID41944347
PMCPMC13271637

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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.