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Author(s): Rita S. Santos
George R. Dakwar
Ranhua Xiong
Katrien Forier
Katrien Remaut
Stephan Stremersch
Nuno Guimarães
Sílvia Fontenete
Jesper Wengel
Marina Leite
Céu Figueiredo
Stefaan C. De Smedt
Kevin Braeckmans
Nuno F. Azevedo
Title: Effect of Native Gastric Mucus on in vivo Hybridization Therapies Directed at Helicobacter pylori
Issue Date: 2015
Abstract: Helicobacter pylori infects more than 50% of the worldwide population. It is mostly found deep in the gastric mucus lining of the stomach, being a major cause of peptic ulcers and gastric adenocarcinoma. To face the increasing resistance of H. pylori to antibiotics, antimicrobial nucleic acid mimics are a promising alternative. In particular, locked nucleic acids (LNA)/2'-OMethyl RNA (2'OMe) have shown to specifically target H. pylori, as evidenced by in situ hybridization. The success of in vivo hybridization depends on the ability of these nucleic acids to penetrate the major physical barriers-the highly viscoelastic gastric mucus and the bacterial cell envelope. We found that LNA/2'OMe is capable of diffusing rapidly through native, undiluted, gastric mucus isolated from porcine stomachs, without degradation. Moreover, although LNA/2'OMe hybridization was still successful without permeabilization and fixation of the bacteria, which is normally part of in vitro studies, the ability of LNA/2'OMe to efficiently hybridize with H. pylori was hampered by the presence of mucus. Future research should focus on developing nanocarriers that shield LNA/2'OMe from components in the gastric mucus, while remaining capable of diffusing through the mucus and delivering these nucleic acid mimics directly into the bacteria.
Related Information: info:eu-repo/grantAgreement/Autoriadade de Gestão do Programa Operacional Regional do Norte/Programas Integrados de IC&DT/NORTE-07-0124-FEDER-000025/(Bio) Chemical Engineering: Multi-Scale Approaches for Sustainable Environment and Health/LEPAE/CEFT - RL2
info:eu-repo/grantAgreement/FCT - Fundação para a Ciência e Tecnologia/Projectos de Investigação Clínica/PIC/IC/82815/2007/Desenvolvimento e aplicação de mímicos de DNA para a rápida identificação de microrganismos patogénicos/DNA mimics
info:eu-repo/grantAgreement/FCT - Fundação para a Ciência e Tecnologia/Projetos Estratégicos/UID/EQU/00511/2013 - POCI-01-0145-FEDER-006939/Laboratório de Engenharia de Processos, Ambiente, Biotecnologia e Energia/LEPABE
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:FEUP - Artigo em Revista Científica Internacional
FMUP - Artigo em Revista Científica Internacional

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