Toxin Neutralization Using Alternative Binding Proteins

Timothy Patrick Jenkins, Thomas Fryer, Rasmus Ibsen Dehli, Jonas Arnold Jürgensen, Albert Fuglsang-Madsen, Sofie Føns, Andreas Hougaard Laustsen*

*Corresponding author for this work

Research output: Contribution to journalReviewResearchpeer-review

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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.
Original languageEnglish
Article number53
JournalToxins
Volume11
Issue number1
Number of pages28
ISSN2072-6651
DOIs
Publication statusPublished - 2019

Keywords

  • Snakebite envenoming
  • Alternative binding protein scaffolds
  • Envenoming therapy
  • Next-generation antivenom
  • Recombinant binding proteins
  • Toxin neutralization
  • Tenom neutralization

Cite this

Jenkins, T. P., Fryer, T., Dehli, R. I., Jürgensen, J. A., Fuglsang-Madsen, A., Føns, S., & Laustsen, A. H. (2019). Toxin Neutralization Using Alternative Binding Proteins. Toxins, 11(1), [53]. https://doi.org/10.3390/toxins11010053
Jenkins, Timothy Patrick ; Fryer, Thomas ; Dehli, Rasmus Ibsen ; Jürgensen, Jonas Arnold ; Fuglsang-Madsen, Albert ; Føns, Sofie ; Laustsen, Andreas Hougaard. / Toxin Neutralization Using Alternative Binding Proteins. In: Toxins. 2019 ; Vol. 11, No. 1.
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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.",
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Jenkins, TP, Fryer, T, Dehli, RI, Jürgensen, JA, Fuglsang-Madsen, A, Føns, S & Laustsen, AH 2019, 'Toxin Neutralization Using Alternative Binding Proteins', Toxins, vol. 11, no. 1, 53. https://doi.org/10.3390/toxins11010053

Toxin Neutralization Using Alternative Binding Proteins. / Jenkins, Timothy Patrick; Fryer, Thomas; Dehli, Rasmus Ibsen; Jürgensen, Jonas Arnold; Fuglsang-Madsen, Albert; Føns, Sofie; Laustsen, Andreas Hougaard.

In: Toxins, Vol. 11, No. 1, 53, 2019.

Research output: Contribution to journalReviewResearchpeer-review

TY - JOUR

T1 - Toxin Neutralization Using Alternative Binding Proteins

AU - Jenkins, Timothy Patrick

AU - Fryer, Thomas

AU - Dehli, Rasmus Ibsen

AU - Jürgensen, Jonas Arnold

AU - Fuglsang-Madsen, Albert

AU - Føns, Sofie

AU - Laustsen, Andreas Hougaard

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Snakebite envenoming

KW - Alternative binding protein scaffolds

KW - Envenoming therapy

KW - Next-generation antivenom

KW - Recombinant binding proteins

KW - Toxin neutralization

KW - Tenom neutralization

U2 - 10.3390/toxins11010053

DO - 10.3390/toxins11010053

M3 - Review

VL - 11

JO - Toxins

JF - Toxins

SN - 2072-6651

IS - 1

M1 - 53

ER -

Jenkins TP, Fryer T, Dehli RI, Jürgensen JA, Fuglsang-Madsen A, Føns S et al. Toxin Neutralization Using Alternative Binding Proteins. Toxins. 2019;11(1). 53. https://doi.org/10.3390/toxins11010053