Genetically engineered red cells expressing single domain camelid antibodies confer long-term protection against botulinum neurotoxin.

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 (LD₅₀) 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

SUBMITTER: Huang NJ 

PROVIDER: S-EPMC5583347 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature