Engineered Escherichia coli for the in situ secretion of therapeutic nanobodies in the gut.

ABSTRACT: Drug platforms that enable the directed delivery of therapeutics to sites of diseases to maximize efficacy and limit off-target effects are needed. Here, we report the development of PROT₃EcT, a suite of commensal Escherichia coli engineered to secrete proteins directly into their surroundings. These bacteria consist of three modular components: a modified bacterial protein secretion system, the associated regulatable transcriptional activator, and a secreted therapeutic payload. PROT₃EcT secrete functional single-domain antibodies, nanobodies (Nbs), and stably colonize and maintain an active secretion system within the intestines of mice. Furthermore, a single prophylactic dose of a variant of PROT₃EcT that secretes a tumor necrosis factor-alpha (TNF-α)-ne

SUBMITTER: Lynch JP 

PROVIDER: S-EPMC10101937 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature