Bacteria engineered to treat diseases that benefit from reduced gut inflammation and/or tighten gut mucosal barrier

摘要

Genetically engineered bacteria, pharmaceutical compositions thereof, and methods of treating or preventing autoimmune disorders, inhibiting inflammatory mechanisms in the gut, and/or tightening gut mucosal barrier function are disclosed.

主权项

1. A genetically engineered bacterium comprising:
a) one or more non-native copies of a first gene that encodes a transcription factor protein that is regulated by a reactive nitrogen species (RNS), wherein the expression of the gene is operatively linked to a promoter; and b) one or more of:
i. a second gene encoding a non-native, anti-inflammation molecule;ii. a second gene encoding a non-native gut barrier function enhancer molecule; andiii. a gene cassette encoding a biosynthetic pathway, wherein the final product of the biosynthetic pathway is an anti-inflammation and/or a barrier function enhancer molecule, whereinthe expression of the second gene or gene cassette in b) is controlled by a tunable regulatory region heterologous to the gene or gene cassette, wherein induction of the tunable regulatory region is directly or indirectly controlled by the transcription factor.