Genetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin
Name
Huang_et_al-2017-Nature_Communications.pdf
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Author(s)
Huang, Nai-Jia
Mukherjee, Jean
Zhang, Sicai
Shoemaker, Charles B.
Pishesha, Novalia
Deshycka, Rhogerry
Sudaryo, Valentino
Lodish, Harvey F
Dong, Min, 1968-
Date Issued
September 2017
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Huang, Nai-Jia et al. “Genetically Engineered Red Cells Expressing Single Domain Camelid Antibodies Confer Long-Term Protection Against Botulinum Neurotoxin.” Nature Communications 8, 1 (September 2017): 423 © 2017 The Author(s)
Version
Final published version
Abstract
A short half-life in the circulation limits the application of therapeutics such as single-domain antibodies (VHHs). We utilize red blood cells to prolong the circulatory half-life of VHHs. Here we present VHHs against botulinum neurotoxin A (BoNT/A) on the surface of red blood cells by expressing chimeric proteins of VHHs with Glycophorin A or Kell. Mice whose red blood cells carry the chimeric proteins exhibit resistance to 10,000 times the lethal dose (LD 50 ) of BoNT/A, and transfusion of these red blood cells into naive mice affords protection for up to 28 days. We further utilize an improved CD34+ culture system to engineer human red blood cells that express these chimeric proteins. Mice transfused with these red blood cells are resistant to highly lethal doses of BoNT/A. We demonstrate that engineered red blood cells expressing VHHs can provide prolonged prophylactic protection against bacterial toxins without inducing inhibitory immune responses and illustrates the potentially broad translatability of our strategy for therapeutic applications.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution 4.0 International
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DOI of Published Version
https://doi.org/10.1038/s41467-017-00448-0
