Thermoresponsive Bacteriophage Nanocarrier as a Gene Delivery Vector Targeted to the Gastrointestinal Tract
Autor: | Paladd Asavarut, Satit Puttipipatkhachorn, Suwimon Boonrungsiman, Mattaka Khongkow, Sasithon Temisak, Katawut Namdee, Amin Hajitou, Naiyaphat Nittayasut, Nattika Saengkrit, Kiat Ruxrungtham, Teerapong Yata |
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Přispěvatelé: | The Leverhulme Trust |
Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Transgene 02 engineering and technology Article Bacteriophage 03 medical and health sciences chemistry.chemical_compound bacteriophage Drug Discovery medicine gene Gene Gastrointestinal tract biology Chemistry lcsh:RM1-950 DNA 021001 nanoscience & nanotechnology biology.organism_classification Epithelium Cell biology 030104 developmental biology medicine.anatomical_structure lcsh:Therapeutics. Pharmacology Filamentous bacteriophage Molecular Medicine nanocarrier gastrointestinal tract Nanocarriers thermoresponsive 0210 nano-technology |
Zdroj: | Molecular Therapy. Nucleic Acids Molecular Therapy: Nucleic Acids, Vol 12, Iss, Pp 33-44 (2018) |
ISSN: | 2162-2531 |
Popis: | 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. Graphical Abstract |
Databáze: | OpenAIRE |
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