RT Journal Article
SR Electronic
T1 <em>In situ</em> reprogramming of gut bacteria by oral delivery
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.15.043232
DO 10.1101/2020.04.15.043232
A1 Hsu, Bryan B.
A1 Plant, Isaac N.
A1 Lyon, Lorena
A1 Anastassacos, Frances M.
A1 Way, Jeffrey C.
A1 Silver, Pamela A.
YR 2020
UL http://biorxiv.org/content/early/2020/04/16/2020.04.15.043232.abstract
AB Abundant links between the gut microbiota and human health indicate that the modification of bacterial function could be a powerful therapeutic strategy. The inaccessibility of the gut and inter-connections between gut bacteria and the host make it difficult to precisely target bacterial functions without disrupting the microbiota and/or host physiology. Herein we describe a multidisciplinary approach to modulate the expression of a specific bacterial gene within the gut by oral administration. We first demonstrate that an engineered temperate phage λ expressing a programmable dCas9 represses a targeted E. coli gene in the mammalian gut. To facilitate phage administration while minimizing disruption to host processes, we develop an aqueous-based encapsulation formulation with a microbiota-based release mechanism and show that it facilitates the oral delivery of phage in vivo. Finally we combine these technologies and show that bacterial gene expression in the mammalian gut can be precisely modified in situ with a single oral dose.Competing Interest StatementThe authors have declared no competing interest.