AI Article Synopsis
- - Botulism is caused by a deadly neurotoxin that disrupts nerve signals, leading to asphyxiation and currently has no antidote or effective treatments.
- - Researchers used a safe form of botulinum neurotoxin to transport a specific antibody inside nerve cells, successfully inhibiting the harmful effects of the toxic type A botulinum neurotoxin in animal models.
- - This method shows promise not only for treating botulism but also for potentially delivering other therapeutic proteins to hard-to-reach areas within neurons in the future.
Article Abstract
Botulism is caused by a potent neurotoxin that blocks neuromuscular transmission, resulting in death by asphyxiation. Currently, the therapeutic options are limited and there is no antidote. Here, we harness the structural and trafficking properties of an atoxic derivative of botulinum neurotoxin (BoNT) to transport a function-blocking single-domain antibody into the neuronal cytosol where it can inhibit BoNT serotype A (BoNT/A1) molecular toxicity. Post-symptomatic treatment relieved toxic signs of botulism and rescued mice, guinea pigs, and nonhuman primates after lethal BoNT/A1 challenge. These data demonstrate that atoxic BoNT derivatives can be harnessed to deliver therapeutic protein moieties to the neuronal cytoplasm where they bind and neutralize intracellular targets in experimental models. The generalizability of this platform might enable delivery of antibodies and other protein-based therapeutics to previously inaccessible intraneuronal targets.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176400 | PMC |
| http://dx.doi.org/10.1126/scitranslmed.abd7789 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Ionizable polymeric micelles (IPMs) for efficient siRNA delivery.
Nat Commun
January 2025
Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, PR China.
Lipid nanoparticles (LNPs) are widely used for nucleic acid delivery but face challenges like limited targeting and accelerated blood clearance (ABC) effect. We design three ionizable oligomers (IOs) that, with polylactide-polyethylene glycol (PLA-PEG), form a potential siRNA delivery system, named Ionizable Polymeric Micelles (IPMs). The siRNA encapsulated IPMs escape from lysosomes upon cellular uptake, and silence the target gene.
View Article and Find Full Text PDFBioactive microspheres to enhance sonodynamic-embolization-metalloimmune therapy for orthotopic liver cancer.
Biomaterials
December 2024
Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon Based Functional Materials & Devices, Soochow University, Suzhou, 215123, China. Electronic address:
The development of novel microspheres for the combination of sonodynamic therapy (SDT) with transarterial embolization (TAE) therapy to amplify their efficacy has received increasing attention. Herein, a novel strategy for encapsulating sonosensitizers (e.g.
View Article and Find Full Text PDFBasic Science and Pathogenesis.
Alzheimers Dement
December 2024
The Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.
Background: Monoclonal antibodies have emerged as a leading therapeutic agent for the treatment of disease, including Alzheimer's disease. Such antibodies, however, are expensive and timely to produce and require frequent dosing regimens to ensure disease-modifying effects. Synthetic in vitro-transcribed mRNA encoding antibodies presents a promising alternative to conventional passive immunotherapy and overcomes the need to generate recombinant antibodies.
View Article and Find Full Text PDFpH-Responsive Polyethylene Glycol Engagers for Enhanced Brain Delivery of PEGylated Nanomedicine to Treat Glioblastoma.
ACS Nano
January 2025
Department of Biological Science and Technology, Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan.
The blood-brain barrier (BBB) remains a major obstacle for effective delivery of therapeutics to treat central nervous system (CNS) disorders. Although transferrin receptor (TfR)-mediated transcytosis is widely employed for brain drug delivery, the inefficient release of therapeutic payload hinders their efficacy from crossing the BBB. Here, we developed a pH-responsive anti-polyethylene glycol (PEG) × anti-TfR bispecific antibody (pH-PEG engager) that can complex with PEGylated nanomedicine at physiological pH to trigger TfR-mediated transcytosis in the brain microvascular endothelial cells, while rapidly dissociating from PEGylated nanomedicine at acidic endosomes for efficient release of PEGylated nanomedicine to cross the BBB.
View Article and Find Full Text PDFPredicting airway immune responses and protection from immune parameters in blood following immunization in a pig influenza model.
Front Immunol
January 2025
Nuffield Department of Medicine, Pandemic Sciences Institute, University of Oxford, Oxford, United Kingdom.
Whereas the intranasally delivered influenza vaccines used in children affect transmission of influenza virus in the community as well as reducing illness, inactivated influenza vaccines administered by intramuscular injection do not prevent transmission and have a variable, sometimes low rate of vaccine effectiveness. Although mucosally administered vaccines have the potential to induce more protective immune response at the site of viral infection, quantitating such immune responses in large scale clinical trials and developing correlates of protection is challenging. Here we show that by using mathematical models immune responses measured in the blood after delivery of vaccine to the lungs by aerosol can predict immune responses in the respiratory tract in pigs.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!