Genetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin
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 c...
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| Format: | Article |
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Nature Publishing Group
2017
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| Online Access: | http://hdl.handle.net/1721.1/112702 https://orcid.org/0000-0001-9306-8271 https://orcid.org/0000-0002-5816-9955 https://orcid.org/0000-0002-7029-7415 |
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| author | Huang, Nai-Jia Mukherjee, Jean Zhang, Sicai Shoemaker, Charles B. Pishesha, Novalia Deshycka, Rhogerry Sudaryo, Valentino Lodish, Harvey F Dong, Min, 1968- |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Huang, Nai-Jia Mukherjee, Jean Zhang, Sicai Shoemaker, Charles B. Pishesha, Novalia Deshycka, Rhogerry Sudaryo, Valentino Lodish, Harvey F Dong, Min, 1968- |
| author_sort | Huang, Nai-Jia |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:28:48Z |
| format | Article |
| id | mit-1721.1/112702 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T10:28:48Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1127022022-09-30T21:24:20Z Genetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin Huang, Nai-Jia Mukherjee, Jean Zhang, Sicai Shoemaker, Charles B. Pishesha, Novalia Deshycka, Rhogerry Sudaryo, Valentino Lodish, Harvey F Dong, Min, 1968- Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Pishesha, Novalia Deshycka, Rhogerry Sudaryo, Valentino Lodish, Harvey F 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. United States. Defense Advanced Research Projects Agency (Contract HR0011-12-2-0015) 2017-12-12T14:46:21Z 2017-12-12T14:46:21Z 2017-09 2016-10 2017-12-11T20:03:50Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/112702 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) https://orcid.org/0000-0001-9306-8271 https://orcid.org/0000-0002-5816-9955 https://orcid.org/0000-0002-7029-7415 http://dx.doi.org/10.1038/s41467-017-00448-0 Nature Communications Creative Commons Attribution 4.0 International https://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature |
| spellingShingle | Huang, Nai-Jia Mukherjee, Jean Zhang, Sicai Shoemaker, Charles B. Pishesha, Novalia Deshycka, Rhogerry Sudaryo, Valentino Lodish, Harvey F Dong, Min, 1968- Genetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin |
| title | Genetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin |
| title_full | Genetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin |
| title_fullStr | Genetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin |
| title_full_unstemmed | Genetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin |
| title_short | Genetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin |
| title_sort | genetically engineered red cells expressing single domain camelid antibodies confer long term protection against botulinum neurotoxin |
| url | http://hdl.handle.net/1721.1/112702 https://orcid.org/0000-0001-9306-8271 https://orcid.org/0000-0002-5816-9955 https://orcid.org/0000-0002-7029-7415 |
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