Delivery of anti-microRNA-21 antisense-oligodeoxynucleotide using amphiphilic peptides for glioblastoma gene therapy
- Authors
- Song, Hojung; Oh, Binna; Choi, Manbok; Oh, Jungju; Lee, Minhyung
- Issue Date
- May-2015
- Publisher
- TAYLOR & FRANCIS LTD
- Keywords
- Amphiphilic peptide; antisense-oligonucleotide; gene therapy; glioblastoma; microRNA-21
- Citation
- JOURNAL OF DRUG TARGETING, v.23, no.4, pp.360 - 370
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF DRUG TARGETING
- Volume
- 23
- Number
- 4
- Start Page
- 360
- End Page
- 370
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/157309
- DOI
- 10.3109/1061186X.2014.1000336
- ISSN
- 1061-186X
- Abstract
- Inhibition of microRNA-21 (miR-21) has been shown to promote apoptosis of cancer cells and to reduce tumor size in glioblastoma. However, efficient carriers for antisense-oligodeoxynucleotide (antisense-ODN) against miR-21 have not yet been developed. In this study, the R3V6 peptide (R3V6) was evaluated as a carrier of antisense-ODN. In a gel retardation assay, R3V6 formed a complex with an antisense-ODN. The serum stability assay showed that R3V6 protected it from nucleases more efficiently than polyethylenimine (PEI; 25 kDa, PEI25k). A Renilla luciferase gene with a 3'-untranslated region (3'-UTR) recognizable by miR-21 (psiCHECK2-miR-21-UTR) was constructed for the antisense-ODN assay. psiCHECK2-miR-21-UTR expressed less Renilla luciferase in the cells with a higher level of miR-21 due to the effect of miR-21. In an in vitro transfection assay, the R3V6 peptide delivered anti-miR-21 antisense-ODN into cells more efficiently than PEI (25 kDa, PEI25k) and lipofectamine. As a result, antisense-ODN/R3V6 complex inhibited miR-21 and increased Renilla luciferase expression more efficiently than antisense-ODN/PEI25k or antisense-ODN/Lipofectamine complexes in both C6 and A172 glioblastoma cells. Furthermore, the antisense-ODN/R3V6 complexes reduced the level of miR-21 and induced apoptosis of glioblastoma cells. These results suggest that the R3V6 peptide may be a useful carrier of antisense-ODN for glioblastoma gene therapy.
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