ArticleProceedings of the National Academy of Sciences of the United States of America2009
Engineering botulinum neurotoxin to extend therapeutic intervention.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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Who cites it
44 citing papers in PubMed, 79 citations in OpenAlex.
- Characterisation of the SNAP-25 and SNAP-23 cleavage properties of the botulinum neurotoxin-like protein from Enterococcus.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- SNAP-47 mediates somatic oxytocin dynamics in hypothalamic neurons.Communications biology · 2026Article
- Protease engineering: Approaches, tools, and emerging trends.Biotechnology advances · 2025Review
- PERRC: Protease Engineering with Reactant Residence Time Control.ACS synthetic biology · 2025Article
- Targeted degradation of α-Synuclein using an evolved botulinum toxin protease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Embracing the Versatility of Botulinum Neurotoxins in Conventional and New Therapeutic Applications.Toxins · 2024Review
- Pathogenicity and virulence ofVirulence · 2023Review
- Botulinum neurotoxins: Future innovations.Medicine · 2023Article
- Reengineering the specificity of the highly selective Clostridium botulinum protease via directed evolution.Scientific reports · 2022Article
- Toxicology and pharmacology of botulinum and tetanus neurotoxins: an update.Archives of toxicology · 2022Review
- Making the cut with protease engineering.Cell chemical biology · 2022Review
- Phage-assisted evolution of botulinum neurotoxin proteases with reprogrammed specificity.Science (New York, N.Y.) · 2021Article
- Novel Native and Engineered Botulinum Neurotoxins.Handbook of experimental pharmacology · 2021Review
- Engineering Botulinum Neurotoxins for Enhanced Therapeutic Applications and Vaccine Development.Toxins · 2020Review
- Article
- KRAS regulation by small non-coding RNAs and SNARE proteins.Nature communications · 2019Article
- Botulinum and Tetanus Neurotoxins.Annual review of biochemistry · 2019Review
- Studying the differential efficacy of postsymptom antitoxin treatment in type A versus type B botulism using a rabbit spirometry model.Disease models & mechanisms · 2018Article
- Engineering Botulinum Toxins to Improve and Expand Targeting and SNARE Cleavage Activity.Toxins · 2018Review
- Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Clostridium botulinum neurotoxins (BoNTs) are effective therapeutics for a variety of neurological disorders, such as strabismus, blepharospam, hemificial spasm, and cervical dystonia, because of the toxin's tropism for neurons and specific cleavage of neuronal soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptors (SNARE) proteins. Modifying BoNT to bind nonneuronal cells has been attempted to extend therapeutic applications. However, prerequisite to develop nonneuronal therapies requires the retargeting the catalytic activity of BoNTs to nonneuronal SNARE isoforms. Here, we reported the engineering of a BoNT derivative that cleaves SNAP23, a nonneuronal SNARE protein. SNAP23 mediates vesicle-plasma membrane fusion processes, including secretion of airway mucus, antibody, insulin, gastric acids, and ions. This mutated BoNT/E light chain LC/E(K(224)D) showed extended substrate specificity to cleave SNAP23, and the natural substrate, SNAP25, but not SNAP29 or SNAP47. Upon direct protein delivery into cultured human epithelial cells, LC/E(K(224)D) cleaved endogenous SNAP23, which inhibited secretion of mucin and IL-8. These studies show the feasibility of genetically modifying LCs to target a nonneuronal SNARE protein that extends therapeutic potential for treatment of human hypersecretion diseases.
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Registered trials
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.