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Thermoresponsive Bacteriophage Nanocarrier as a Gene Delivery Vector Targeted to the Gastrointestinal Tract
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Metadata
Document Title
Thermoresponsive Bacteriophage Nanocarrier as a Gene Delivery Vector Targeted to the Gastrointestinal Tract
Author
Namdee K.,Khongkow M.,Boonrungsiman S.,Nittayasut N.,Asavarut P.,Temisak S.,Saengkrit N.,Puttipipatkhachorn S.,Hajitou A.,Ruxrungtham K.,Yata T.
Name from Authors Collection
Affiliations
National Nanotechnology Centre (NANOTEC), National Science and Technology Development Agency, Pathumthani, Thailand; Cancer Phage Therapy Group, Division of Brain Sciences, Imperial College London, London, United Kingdom; Bio Analysis Group, Chemical Metrology and Biometry Department, National Institute of Metrology (NIMT), Pathumthani, Thailand; Department of Manufacturing Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand; Vaccine and Cellular Immunology Laboratory, Vaccine Research Center (ChulaVRC) and Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Type
Article
Source Title
Molecular Therapy - Nucleic Acids
ISSN
21622531
Year
2018
Volume
12
Open Access
All Open Access, Gold, Green
Publisher
Cell Press
DOI
10.1016/j.omtn.2018.04.012
Abstract
The use of the gastrointestinal tract as a site for the local delivery of DNA is an exciting prospect. In order to obtain an effective vector capable of delivering a gene of interest to target cells to achieve sufficient and sustained transgene expression, with minimal toxicity, we developed a new generation of filamentous bacteriophage. This particular bacteriophage was genetically engineered to display an arginine-glycine-aspartic acid (RGD) motif (an integrin-binding peptide) on the major coat protein pVIII and carry a mammalian DNA cassette. One unanticipated observation is the thermoresponsive behavior of engineered bacteriophage. This finding has led us to simplify the isolation method to purify bacteriophage particles from cell culture supernatant by low-temperature precipitation. Our results showed that, in contrast to non-surface modified, the RGD-modified bacteriophage was successfully used to deliver a transgene to mammalian cells. Our in vitro model of the human intestinal follicle-associated epithelium also demonstrated that bacteriophage particles were stable in simulated gastrointestinal fluids and able to cross the human intestinal barrier. In addition, we confirmed an adjuvant property of the engineered bacteriophage to induce nitric oxide production by macrophages. In conclusion, our study demonstrated the possibility of using bacteriophage for gene transfer in the gastrointestinal tract. © 2018 The Author(s)
Keyword
Bacteriophage | DNA | gastrointestinal tract | gene | nanocarrier | thermoresponsive
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
National Science and Technology Development Agency; Thailand Research Fund; National Nanotechnology Center
License
CC BY-NC-ND
Rights
Elsevier B.V.
Publication Source
Scopus