siRNA--getting the message out.
The recent observation that potent and sequence-specific gene silencing by injection of double-stranded RNA (dsRNA) has sparked the phenomenon known as "RNA interference" (RNAi) and has enabled the gene-specific knockdown of drug transport proteins and metabolizing enzymes. The application of small interfering RNAs (siRNAs) is broad and the potential for use as research tools is now well established in vitro. In vivo use is still a challenge that is primarily focused on the difficulty of delivering siRNAs to target cells. The potential use of siRNAs as therapeutic agents is also exciting and holds great promise for future. For the study of drug transporter function in absorption, distribution, metabolism and excretion (ADME) and in the treatment of diseases, siRNA offers a way to gather interpretable mechanistic data-a distinct advantage over the use of "specific" chemical inhibitors. This mini review provides background information on siRNA as well as examples of the use of siRNA as applied to drug transporters.
Lee
S H
SH
Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
Sinko
P J
PJ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018938:Caco-2 Cells; D004077:Digoxin / Q000378:metabolism; D018390:Gene Targeting; D015316:Genetic Therapy; D006801:Humans; D049410:Luciferases, Renilla; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D014162:Transfection
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D034741:RNA, Small Interfering; D004077:Digoxin; D049410:Luciferases, Renilla