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.
Heme oxygenase-1 (HO-1) has anti-apoptotic and anti-inflammatory effects. In this study, the HO-1 gene was delivered into the brain using dexamethasone-conjugated polyamidoamine generation 2 (PAMAM G2-Dexa) for the treatment of ischemic stroke. PAMAM G2-Dexa formed stable complexes with plasmid DNA (pDNA). The pDNA delivery efficiency of PAMAM G2-Dexa was higher than that of polyethylenimine (PEI25k, 25 kDa), dexamethasone-conjugated PEI (PEI-Dexa), and PAMAM G2 in Neuro2A cells. Therapeutic effect of PAMAM G2-Dexa/pHO-1 complexes was evaluated in a stroke animal model. PAMAM G2-Dexa delivered pHO-1 more efficiently into the ischemic brain than PEI25k and PEI-Dexa with higher therapeutic effect. Therefore, PAMAM G2-Dexa/pHO-1 complexes may be useful for ischemic stroke gene therapy.
pEpo-SV-HO-1 induced HO-1 gene expression and therapeutic effect in the ischemic brain. Therefore, pEpo-SV-HO-1 may be useful for site-specific gene therapy of ischemic stroke.
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