| RRC ID |
44380
|
| Author |
Sakurai Y, Hatakeyama H, Sato Y, Hyodo M, Akita H, Harashima H.
|
| Title |
Gene silencing via RNAi and siRNA quantification in tumor tissue using MEND, a liposomal siRNA delivery system.
|
| Journal |
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.
|
| Volume |
21(6)
|
| Pages |
1195-203
|
| Published |
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
|
| Times Cited |
82
|
|
WOS Category
|
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
MEDICINE, RESEARCH & EXPERIMENTAL
GENETICS & HEREDITY
|
| Resource |
| Human and Animal Cells |
OS-RC-2(RCB0735) |
