Toxin Neutralization Using Alternative Binding Proteins.


Type
Article
Change log
Authors
Jenkins, Timothy Patrick  ORCID logo  https://orcid.org/0000-0003-2979-5663
Dehli, Rasmus Ibsen 
Jürgensen, Jonas Arnold 
Fuglsang-Madsen, Albert 
Abstract

Animal toxins present a major threat to human health worldwide, predominantly through snakebite envenomings, which are responsible for over 100,000 deaths each year. To date, the only available treatment against snakebite envenoming is plasma-derived antivenom. However, despite being key to limiting morbidity and mortality among snakebite victims, current antivenoms suffer from several drawbacks, such as immunogenicity and high cost of production. Consequently, avenues for improving envenoming therapy, such as the discovery of toxin-sequestering monoclonal antibodies against medically important target toxins through phage display selection, are being explored. However, alternative binding protein scaffolds that exhibit certain advantages compared to the well-known immunoglobulin G scaffold, including high stability under harsh conditions and low cost of production, may pose as possible low-cost alternatives to antibody-based therapeutics. There is now a plethora of alternative binding protein scaffolds, ranging from antibody derivatives (e.g., nanobodies), through rationally designed derivatives of other human proteins (e.g., DARPins), to derivatives of non-human proteins (e.g., affibodies), all exhibiting different biochemical and pharmacokinetic profiles. Undeniably, the high level of engineerability and potentially low cost of production, associated with many alternative protein scaffolds, present an exciting possibility for the future of snakebite therapeutics and merit thorough investigation. In this review, a comprehensive overview of the different types of binding protein scaffolds is provided together with a discussion on their relevance as potential modalities for use as next-generation antivenoms.

Description
Keywords
Snakebite envenoming, alternative binding protein scaffolds, envenoming therapy, next-generation antivenom, recombinant binding proteins, toxin neutralization, venom neutralization, Animals, Antibodies, Monoclonal, Antitoxins, Bites and Stings, Carrier Proteins, Humans, Immunization, Passive, Toxins, Biological
Journal Title
Toxins (Basel)
Conference Name
Journal ISSN
2072-6651
2072-6651
Volume Title
11
Publisher
MDPI AG
Sponsorship
Biotechnology and Biological Sciences Research Council (1651279)