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Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins

Research output: Contribution to Journal/Magazine › Journal article › peer-review

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Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins. / Khalek, Irene S.; Laxme, R. R.Senji; Nguyen, Yen Thi Kim et al.
In: Science Translational Medicine, Vol. 16, No. 735, eadk1867, 21.02.2024.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Khalek, IS, Laxme, RRS, Nguyen, YTK, Khochare, S, Patel, RN, Woehl, J, Smith, JM, Saye-Francisco, K, Kim, Y, Mindrebo, LM, Tran, Q, Kędzior, M, Boré, E, Limbo, O, Verma, M, Stanfield, RL, Menzies, SK, Ainsworth, S, Harrison, RA, Burton, DR, Sok, D, Wilson, IA, Casewell, NR, Sunagar, K & Jardine, JG 2024, 'Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins', Science Translational Medicine, vol. 16, no. 735, eadk1867. https://doi.org/10.1126/scitranslmed.adk1867

APA

Khalek, I. S., Laxme, R. R. S., Nguyen, Y. T. K., Khochare, S., Patel, R. N., Woehl, J., Smith, J. M., Saye-Francisco, K., Kim, Y., Mindrebo, L. M., Tran, Q., Kędzior, M., Boré, E., Limbo, O., Verma, M., Stanfield, R. L., Menzies, S. K., Ainsworth, S., Harrison, R. A., ... Jardine, J. G. (2024). Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins. Science Translational Medicine, 16(735), Article eadk1867. https://doi.org/10.1126/scitranslmed.adk1867

Vancouver

Khalek IS, Laxme RRS, Nguyen YTK, Khochare S, Patel RN, Woehl J et al. Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins. Science Translational Medicine. 2024 Feb 21;16(735):eadk1867. doi: 10.1126/scitranslmed.adk1867

Author

Khalek, Irene S. ; Laxme, R. R.Senji ; Nguyen, Yen Thi Kim et al. / Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins. In: Science Translational Medicine. 2024 ; Vol. 16, No. 735.

Bibtex

@article{507605eaf04d4f799ae7d28f452bb955,
title = "Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins",
abstract = "Snakebite envenoming is a major global public health concern for which improved therapies are urgently needed. The antigenic diversity present in snake venom toxins from various species presents a considerable challenge to the development of a universal antivenom. Here, we used a synthetic human antibody library to find and develop an antibody that neutralizes long-chain three-finger α-neurotoxins produced by numerous medically relevant snakes. our antibody bound diverse toxin variants with high affinity, blocked toxin binding to the nicotinic acetylcholine receptor in vitro, and protected mice from lethal venom challenge. structural analysis of the antibody-toxin complex revealed a binding mode that mimics the receptor-toxin interaction. The overall workflow presented is generalizable for the development of antibodies that target conserved epitopes among antigenically diverse targets, and it offers a promising framework for the creation of a monoclonal antibody–based universal antivenom to treat snakebite envenoming.",
author = "Khalek, {Irene S.} and Laxme, {R. R.Senji} and Nguyen, {Yen Thi Kim} and Suyog Khochare and Patel, {Rohit N.} and Jordan Woehl and Smith, {Jessica M.} and Karen Saye-Francisco and Yoojin Kim and Mindrebo, {Laetitia Misson} and Quoc Tran and Mateusz K{\c e}dzior and Evy Bor{\'e} and Oliver Limbo and Megan Verma and Stanfield, {Robyn L.} and Menzies, {Stefanie K.} and Stuart Ainsworth and Harrison, {Robert A.} and Burton, {Dennis R.} and Devin Sok and Wilson, {Ian A.} and Casewell, {Nicholas R.} and Kartik Sunagar and Jardine, {Joseph G.}",
note = "Publisher Copyright: {\textcopyright} 2024 The Authors, some rights reserved.",
year = "2024",
month = feb,
day = "21",
doi = "10.1126/scitranslmed.adk1867",
language = "English",
volume = "16",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "735",

}

RIS

TY - JOUR

T1 - Synthetic development of a broadly neutralizing antibody against snake venom long-chain α-neurotoxins

AU - Khalek, Irene S.

AU - Laxme, R. R.Senji

AU - Nguyen, Yen Thi Kim

AU - Khochare, Suyog

AU - Patel, Rohit N.

AU - Woehl, Jordan

AU - Smith, Jessica M.

AU - Saye-Francisco, Karen

AU - Kim, Yoojin

AU - Mindrebo, Laetitia Misson

AU - Tran, Quoc

AU - Kędzior, Mateusz

AU - Boré, Evy

AU - Limbo, Oliver

AU - Verma, Megan

AU - Stanfield, Robyn L.

AU - Menzies, Stefanie K.

AU - Ainsworth, Stuart

AU - Harrison, Robert A.

AU - Burton, Dennis R.

AU - Sok, Devin

AU - Wilson, Ian A.

AU - Casewell, Nicholas R.

AU - Sunagar, Kartik

AU - Jardine, Joseph G.

N1 - Publisher Copyright: © 2024 The Authors, some rights reserved.

PY - 2024/2/21

Y1 - 2024/2/21

N2 - Snakebite envenoming is a major global public health concern for which improved therapies are urgently needed. The antigenic diversity present in snake venom toxins from various species presents a considerable challenge to the development of a universal antivenom. Here, we used a synthetic human antibody library to find and develop an antibody that neutralizes long-chain three-finger α-neurotoxins produced by numerous medically relevant snakes. our antibody bound diverse toxin variants with high affinity, blocked toxin binding to the nicotinic acetylcholine receptor in vitro, and protected mice from lethal venom challenge. structural analysis of the antibody-toxin complex revealed a binding mode that mimics the receptor-toxin interaction. The overall workflow presented is generalizable for the development of antibodies that target conserved epitopes among antigenically diverse targets, and it offers a promising framework for the creation of a monoclonal antibody–based universal antivenom to treat snakebite envenoming.

AB - Snakebite envenoming is a major global public health concern for which improved therapies are urgently needed. The antigenic diversity present in snake venom toxins from various species presents a considerable challenge to the development of a universal antivenom. Here, we used a synthetic human antibody library to find and develop an antibody that neutralizes long-chain three-finger α-neurotoxins produced by numerous medically relevant snakes. our antibody bound diverse toxin variants with high affinity, blocked toxin binding to the nicotinic acetylcholine receptor in vitro, and protected mice from lethal venom challenge. structural analysis of the antibody-toxin complex revealed a binding mode that mimics the receptor-toxin interaction. The overall workflow presented is generalizable for the development of antibodies that target conserved epitopes among antigenically diverse targets, and it offers a promising framework for the creation of a monoclonal antibody–based universal antivenom to treat snakebite envenoming.

U2 - 10.1126/scitranslmed.adk1867

DO - 10.1126/scitranslmed.adk1867

M3 - Journal article

C2 - 38381847

AN - SCOPUS:85185619790

VL - 16

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 735

M1 - eadk1867

ER -