Nonpathogenic-invasive Escherichia coli (InvColi) bacteria are suitable for genetic transfer into mammalian cells and may act as a vehicle for RNA Interference (RNAi) in vivo. Cyclooxygenase-2 (COX-2) is overexpressed in ulcerative colitis (UC) and Crohn’s disease (CD), two inflammatory conditions of the colon and small intestine grouped as inflammatory bowel disease (IBD). We engineered InvColi strains for anti-COX-2 RNAi (InvColishCOX2), aiming to investigate the in vivo feasibility of a novel COX-2 silencing strategy in a murine model of colitis induced by dextran sulfate sodium (DSS). Enema administrations of InvColishCOX2 in DSS-treated mice led to COX-2 downregulation, colonic mucosa preservation, reduced colitis disease activity index (DAI) and increased mice survival. Moreover, DSS/InvColishCOX2-treated mice showed lower levels of circulating pro-inflammatory cytokines and a reduced colitis-associated shift of gut microbiota. Considering its effectiveness and safety, we propose our InvColishCOX2 strategy as a promising tool for molecular therapy in intestinal inflammatory diseases.

Nonpathogenic-invasive Escherichia coli (InvColi) bacteria are suitable for genetic transfer into mammalian cells and may act as a vehicle for RNA Interference (RNAi) in viva Cyclooxygenase-2 (COX-2) is overexpressed in ulcerative colitis (UC) and Crohn's disease (CD), two inflammatory conditions of the colon and small intestine grouped as inflammatory bowel disease (IBD). We engineered Inv Coll strains for anti-COX-2 RNAi (InvColi(shCOX2)), aiming to investigate the in vivo feasibility of a novel COX-2 silencing strategy in a murine model of colitis induced by dextran sulfate sodium (DSS). Enema administrations of InvColi(shCOX2) in DSS-treated mice led to COX-2 downregulation, colonic mucosa preservation, reduced colitis disease activity index (DAI) and increased mice survival. Moreover, DSS/InvColi(shCOX2)- treated mice showed lower levels of circulating pro-inflammatory cytokines and a reduced colitis-associated shift of gut microbiota. Considering its effectiveness and safety, we propose our InvColi(shCOX2) strategy as a promising tool for molecular therapy in intestinal inflammatory diseases.

Cyclooxygenase-2 Silencing for the Treatment of Colitis: A Combined In Vivo Strategy Based on RNA Interference and Engineered Escherichia Coli / Enzo Spisni; Maria C Valerii; Luigia De Fazio; Elena Cavazza; Francesca Borsetti; Annamaria Sgromo; Marco Candela; Manuela Centanni; Fernando Rizzello; Antonio Strillacci. - In: MOLECULAR THERAPY. - ISSN 1525-0016. - STAMPA. - 23:2(2015), pp. 278-289. [10.1038/mt.2014.222]

Cyclooxygenase-2 Silencing for the Treatment of Colitis: A Combined In Vivo Strategy Based on RNA Interference and Engineered Escherichia Coli

SPISNI, ENZO;VALERII, MARIA CHIARA;DE FAZIO, LUIGIA;CAVAZZA, ELENA;BORSETTI, FRANCESCA;CANDELA, MARCO;CENTANNI, MANUELA;RIZZELLO, FERNANDO;STRILLACCI, ANTONIO
2015

Abstract

Nonpathogenic-invasive Escherichia coli (InvColi) bacteria are suitable for genetic transfer into mammalian cells and may act as a vehicle for RNA Interference (RNAi) in viva Cyclooxygenase-2 (COX-2) is overexpressed in ulcerative colitis (UC) and Crohn's disease (CD), two inflammatory conditions of the colon and small intestine grouped as inflammatory bowel disease (IBD). We engineered Inv Coll strains for anti-COX-2 RNAi (InvColi(shCOX2)), aiming to investigate the in vivo feasibility of a novel COX-2 silencing strategy in a murine model of colitis induced by dextran sulfate sodium (DSS). Enema administrations of InvColi(shCOX2) in DSS-treated mice led to COX-2 downregulation, colonic mucosa preservation, reduced colitis disease activity index (DAI) and increased mice survival. Moreover, DSS/InvColi(shCOX2)- treated mice showed lower levels of circulating pro-inflammatory cytokines and a reduced colitis-associated shift of gut microbiota. Considering its effectiveness and safety, we propose our InvColi(shCOX2) strategy as a promising tool for molecular therapy in intestinal inflammatory diseases.
2015
Cyclooxygenase-2 Silencing for the Treatment of Colitis: A Combined In Vivo Strategy Based on RNA Interference and Engineered Escherichia Coli / Enzo Spisni; Maria C Valerii; Luigia De Fazio; Elena Cavazza; Francesca Borsetti; Annamaria Sgromo; Marco Candela; Manuela Centanni; Fernando Rizzello; Antonio Strillacci. - In: MOLECULAR THERAPY. - ISSN 1525-0016. - STAMPA. - 23:2(2015), pp. 278-289. [10.1038/mt.2014.222]
Enzo Spisni; Maria C Valerii; Luigia De Fazio; Elena Cavazza; Francesca Borsetti; Annamaria Sgromo; Marco Candela; Manuela Centanni; Fernando Rizzello; Antonio Strillacci
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/404975
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