Thermoresponsive Bacteriophage Nanocarrier as a Gene Delivery Vector Targeted to the Gastrointestinal Tract

Thermoresponsive Bacteriophage Nanocarrier as a Gene Delivery Vector Targeted to the Gastrointestinal Tract

© 2018 The Author(s) 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,...

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Bibliographic Details
Main Authors: Katawut Namdee, Mattaka Khongkow, Suwimon Boonrungsiman, Naiyaphat Nittayasut, Paladd Asavarut, Sasithon Temisak, Nattika Saengkrit, Satit Puttipipatkhachorn, Amin Hajitou, Kiat Ruxrungtham, Teerapong Yata
Other Authors: Chulalongkorn University
Format: Article
Published: 2019
Subjects:
Biochemistry, Genetics and Molecular Biology
Pharmacology, Toxicology and Pharmaceutics
Online Access:https://repository.li.mahidol.ac.th/handle/123456789/45053
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Institution: Mahidol University
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Summary:© 2018 The Author(s) 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.

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