論文 - 詳細
| RRC ID | 44380 |
|---|---|
| 著者 | Sakurai Y, Hatakeyama H, Sato Y, Hyodo M, Akita H, Harashima H. |
| タイトル | Gene silencing via RNAi and siRNA quantification in tumor tissue using MEND, a liposomal siRNA delivery system. |
| ジャーナル | Mol Ther |
| Abstract |
Small interfering RNA (siRNA) would be predicted to function as a cancer drug, but an efficient siRNA delivery system is required for clinical development. To address this issue, we developed a liposomal siRNA carrier, a multifunctional envelope-type nanodevice (MEND). We previously reported that a MEND composed of a pH-sensitive cationic lipid, YSK05, showed significant knockdown in both in vitro and in tumor tissue by intratumoral injection. Here, we report on the development of an in vivo siRNA delivery system that is delivered by systemic injection and an analysis of the pharmacokinetics of an intravenously administered siRNA molecule in tumor tissue. Tumor delivery of siRNA was quantified by means of stem-loop primer quantitative reverse transcriptase PCR (qRT-PCR) method. PEGylation of the YSK-MEND results in the increase in the accumulation of siRNA in tumor tissue from 0.0079% ID/g tumor to 1.9% ID/g tumor. The Administration of the MEND (3 mg siRNA/kg body weight) showed about a 50% reduction in the target gene mRNA and protein. Moreover, we verified the induction of RNA interference by 5' RACE-PCR method. The collective results reported here indicate that an siRNA carrier was developed that can deliver siRNA to a target cell in tumor tissue through an improved siRNA bioavailability. |
| 巻・号 | 21(6) |
| ページ | 1195-203 |
| 公開日 | 2013-6-1 |
| DOI | 10.1038/mt.2013.57 |
| PII | S1525-0016(16)32613-2 |
| PMID | 23568259 |
| PMC | PMC3677313 |
| MeSH | Administration, Intravenous Amino Acid Sequence Animals Cell Line, Tumor Gene Transfer Techniques* Humans Lipids / pharmacology Liposomes / chemistry* Male Mice Mice, Inbred BALB C Mice, Inbred ICR Microscopy, Confocal Molecular Sequence Data Neoplasms / therapy* Piperidines / pharmacology Polyethylene Glycols / metabolism RNA Interference* RNA, Messenger / antagonists & inhibitors RNA, Messenger / genetics RNA, Messenger / metabolism RNA, Small Interfering / administration & dosage* Toxicity Tests |
| IF | 8.986 |
| 引用数 | 82 |
| WOS 分野 | BIOTECHNOLOGY & APPLIED MICROBIOLOGY MEDICINE, RESEARCH & EXPERIMENTAL GENETICS & HEREDITY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | OS-RC-2(RCB0735) |