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Effect of native gastric mucus on in vivo hybridization therapies directed at Helicobacter pylori

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Center for nano- and biophotonics (NB-Photonics)
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.
Keywords
fluorescence in situ hybridization, locked nucleic acid, Helicobacter pylori, native gastric mucus, 2 '-OMethyl RNA, NUCLEIC-ACID PROBE, LASER-SCANNING MICROSCOPE, SITU HYBRIDIZATION, ANTISENSE OLIGONUCLEOTIDES, NONHUMAN-PRIMATES, IDENTIFICATION, INFECTION, FISH, CELLS, MICROORGANISMS

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Chicago
Santos, Rita, George Dakwar, Ranhua Xiong, Katrien Forier, Katrien Remaut, Stephan Stremersch, Nuno Guimarães, et al. 2015. “Effect of Native Gastric Mucus on in Vivo Hybridization Therapies Directed at Helicobacter Pylori.” Molecular Therapy-nucleic Acids 4.
APA
Santos, R., Dakwar, G., Xiong, R., Forier, K., Remaut, K., Stremersch, S., Guimarães, N., et al. (2015). Effect of native gastric mucus on in vivo hybridization therapies directed at Helicobacter pylori. MOLECULAR THERAPY-NUCLEIC ACIDS, 4.
Vancouver
1.
Santos R, Dakwar G, Xiong R, Forier K, Remaut K, Stremersch S, et al. Effect of native gastric mucus on in vivo hybridization therapies directed at Helicobacter pylori. MOLECULAR THERAPY-NUCLEIC ACIDS. 2015;4.
MLA
Santos, Rita, George Dakwar, Ranhua Xiong, et al. “Effect of Native Gastric Mucus on in Vivo Hybridization Therapies Directed at Helicobacter Pylori.” MOLECULAR THERAPY-NUCLEIC ACIDS 4 (2015): n. pag. Print.
@article{7244714,
  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.},
  articleno    = {e269},
  author       = {Santos, Rita and Dakwar, George and Xiong, Ranhua and Forier, Katrien and Remaut, Katrien and Stremersch, Stephan and Guimar{\~a}es, Nuno and Fontenete, Silvia and Wengel, Jesper and Leite, Marina and Figueiredo, C{\'e}u and De Smedt, Stefaan and Braeckmans, Kevin and Azevedo, Nuno F},
  issn         = {2162-2531},
  journal      = {MOLECULAR THERAPY-NUCLEIC ACIDS},
  keyword      = {fluorescence in situ hybridization,locked nucleic acid,Helicobacter pylori,native gastric mucus,2 '-OMethyl RNA,NUCLEIC-ACID PROBE,LASER-SCANNING MICROSCOPE,SITU HYBRIDIZATION,ANTISENSE OLIGONUCLEOTIDES,NONHUMAN-PRIMATES,IDENTIFICATION,INFECTION,FISH,CELLS,MICROORGANISMS},
  language     = {eng},
  pages        = {9},
  title        = {Effect of native gastric mucus on in vivo hybridization therapies directed at Helicobacter pylori},
  url          = {http://dx.doi.org/10.1038/mtna.2015.46},
  volume       = {4},
  year         = {2015},
}

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