Functionalization of endogenous bacteria
Various aspects and embodiments of the present disclosure are directed to methods and compositions for functionalizing endogenous bacteria in vivo. The methods include delivering to endogenous bacterial cells a recombinant bacteriophage or phagemid that is engineered to contain at least one genetic circuit.
1. A method of functionalizing endogenous Escherichia coli ( E. coli ) in a subject, the method comprising delivering to a subject having an inflammatory bowel disease, non-lytic recombinant Inoviridae M13 coliphage that
are not comprised within a bacterial cell during delivery,
infect viable nonpathogenic endogenous E. coli present in the subject, and
are engineered to contain at least one nucleic acid comprising an inducible promoter operably linked to a nucleotide sequence that encodes an interleukin (IL),
to produce viable nonpathogenic functionalized E. coli in the subject.
2. The method of claim 1 , wherein the inflammatory bowel disease is Crohn's disease.
3. The method of claim 1 , wherein the IL is IL-4.
4. The method of claim 1 , wherein the inflammatory bowel disease is ulcerative colitis.
5. The method of claim 1 , wherein the IL is IL-6.
6. The method of claim 1 , wherein the IL is IL-10.
7. The method of claim 1 , wherein the IL is IL-11.
8. The method of claim 1 , wherein the IL is IL-13.