An attempt to develop non-viral gene therapy for advanced pancreatic cancer.

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Pancreatic cancer is adisease with an extremely poor prognosis, but gene therapy, a totally novel treatment modality, is emerging as a potential treatment for curing such an intractable disese. In this study, an attempt is made to develop non-viral gene therapy for advanced pancreatic cancer through use of RNA interference (RNAi) and a tumor-targeting peptide vector, CRGDCF(K[H-]KKK)6.In general, the sequence-specific RNAi effect in the case of long double-stranded RNAs (dsRNAs) can be masked in commom mammalian cells because of their well-developed interferon response to dsRNAs, In human cancer cell lines, the RNAi (or RNAi-like) effect was observed even by long dsRNAs (Clin ExpPharrnacolPhysiol30: 96, 2003), being approximately two-fold more potent than the antisense RNA effect. Small interfering RNAs (siRNAs), duplexes of 21 nt RNA with 2 nt 3' overhangs, are short enough for evading the interferon response but long enough for inducing the RNAi effect. With Oligofectamine for transfection, the RNAi effect was observed in human leukemia cell lines (Cancer Gene Ther 10: 125, 2003). Although the efficiency was not so high compared with that with Oligofectamine, the peptide vector was observed to function as a carrier for siRNAs as wellas antisense oligonucleotides (Clin Exp Pharmacol Physiol 30: 96, 2003). The peptide vector and siRNA is supposed to electrostatically form a complex in a 1 to 1 molar ratio. Further studies are being planned to improve such a tumor-targeting gene therapy.