Small interfering RNA in drug metabolism and transport

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

RNA interference (RNAi) is a powerful technique that utilizes RNA molecules to specifically knock down the expression of targeted gene at posttranscriptional level. These small interfering RNAs (siRNAs) not only have broad application to basic biomedical research but may be developed as therapeutic agents. Drug-metabolizing enzymes (DMEs) and drug transporters (DTs) are molecular determinants of pharmacokinetic property of a drug. Transcriptional gene expression of DMEs and DTs is controlled by xenobiotic-sensing nuclear receptors (NRs). Because of complexity in studying the function of individual DMEs, DTs and Nits, siRNAs can be an excellent addition to chemical inhibitors and inhibitory antibodies in delineating their specific roles in drug metabolism and transport, gene regulation, and drug-drug interactions. RNAi may be employed to modulate DT expression to overcome multidrug resistance. Recent studies using RNAi to silence gene expression of specific DME, DT and NR, and the impact on drug metabolism and transport are discussed in this review. Concerns remain about the efficiency, specificity, and off-target effects when interpreting data obtained from RNAi studies. Furthermore, potential role for endogenous siRNAs, microRNA (miRNA) molecules, in controlling the posttranscriptional gene regulation of DMEs, DTs and NRs is discussed.

Original languageEnglish (US)
Pages (from-to)700-708
Number of pages9
JournalCurrent Drug Metabolism
Volume8
Issue number7
DOIs
StatePublished - Oct 2007
Externally publishedYes

Fingerprint

Metabolism
Small Interfering RNA
Pharmaceutical Preparations
RNA Interference
Cytoplasmic and Nuclear Receptors
Gene expression
Drug Receptors
Enzymes
RNA
Drug and Narcotic Control
Gene Expression
Pediculus
Multiple Drug Resistance
Xenobiotics
Drug interactions
MicroRNAs
Drug Interactions
Genes
Molecules
Pharmacokinetics

Keywords

  • Drug metabolism and transport
  • Enzyme
  • Gene regulation
  • miRNA
  • Nuclear receptor
  • RNAi
  • siRNA
  • Transporter

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Small interfering RNA in drug metabolism and transport. / Yu, Aiming.

In: Current Drug Metabolism, Vol. 8, No. 7, 10.2007, p. 700-708.

Research output: Contribution to journalArticle

@article{7aa305504411405da678f1b72c9bf6f3,
title = "Small interfering RNA in drug metabolism and transport",
abstract = "RNA interference (RNAi) is a powerful technique that utilizes RNA molecules to specifically knock down the expression of targeted gene at posttranscriptional level. These small interfering RNAs (siRNAs) not only have broad application to basic biomedical research but may be developed as therapeutic agents. Drug-metabolizing enzymes (DMEs) and drug transporters (DTs) are molecular determinants of pharmacokinetic property of a drug. Transcriptional gene expression of DMEs and DTs is controlled by xenobiotic-sensing nuclear receptors (NRs). Because of complexity in studying the function of individual DMEs, DTs and Nits, siRNAs can be an excellent addition to chemical inhibitors and inhibitory antibodies in delineating their specific roles in drug metabolism and transport, gene regulation, and drug-drug interactions. RNAi may be employed to modulate DT expression to overcome multidrug resistance. Recent studies using RNAi to silence gene expression of specific DME, DT and NR, and the impact on drug metabolism and transport are discussed in this review. Concerns remain about the efficiency, specificity, and off-target effects when interpreting data obtained from RNAi studies. Furthermore, potential role for endogenous siRNAs, microRNA (miRNA) molecules, in controlling the posttranscriptional gene regulation of DMEs, DTs and NRs is discussed.",
keywords = "Drug metabolism and transport, Enzyme, Gene regulation, miRNA, Nuclear receptor, RNAi, siRNA, Transporter",
author = "Aiming Yu",
year = "2007",
month = "10",
doi = "10.2174/138920007782109751",
language = "English (US)",
volume = "8",
pages = "700--708",
journal = "Current Drug Metabolism",
issn = "1389-2002",
publisher = "Bentham Science Publishers B.V.",
number = "7",

}

TY - JOUR

T1 - Small interfering RNA in drug metabolism and transport

AU - Yu, Aiming

PY - 2007/10

Y1 - 2007/10

N2 - RNA interference (RNAi) is a powerful technique that utilizes RNA molecules to specifically knock down the expression of targeted gene at posttranscriptional level. These small interfering RNAs (siRNAs) not only have broad application to basic biomedical research but may be developed as therapeutic agents. Drug-metabolizing enzymes (DMEs) and drug transporters (DTs) are molecular determinants of pharmacokinetic property of a drug. Transcriptional gene expression of DMEs and DTs is controlled by xenobiotic-sensing nuclear receptors (NRs). Because of complexity in studying the function of individual DMEs, DTs and Nits, siRNAs can be an excellent addition to chemical inhibitors and inhibitory antibodies in delineating their specific roles in drug metabolism and transport, gene regulation, and drug-drug interactions. RNAi may be employed to modulate DT expression to overcome multidrug resistance. Recent studies using RNAi to silence gene expression of specific DME, DT and NR, and the impact on drug metabolism and transport are discussed in this review. Concerns remain about the efficiency, specificity, and off-target effects when interpreting data obtained from RNAi studies. Furthermore, potential role for endogenous siRNAs, microRNA (miRNA) molecules, in controlling the posttranscriptional gene regulation of DMEs, DTs and NRs is discussed.

AB - RNA interference (RNAi) is a powerful technique that utilizes RNA molecules to specifically knock down the expression of targeted gene at posttranscriptional level. These small interfering RNAs (siRNAs) not only have broad application to basic biomedical research but may be developed as therapeutic agents. Drug-metabolizing enzymes (DMEs) and drug transporters (DTs) are molecular determinants of pharmacokinetic property of a drug. Transcriptional gene expression of DMEs and DTs is controlled by xenobiotic-sensing nuclear receptors (NRs). Because of complexity in studying the function of individual DMEs, DTs and Nits, siRNAs can be an excellent addition to chemical inhibitors and inhibitory antibodies in delineating their specific roles in drug metabolism and transport, gene regulation, and drug-drug interactions. RNAi may be employed to modulate DT expression to overcome multidrug resistance. Recent studies using RNAi to silence gene expression of specific DME, DT and NR, and the impact on drug metabolism and transport are discussed in this review. Concerns remain about the efficiency, specificity, and off-target effects when interpreting data obtained from RNAi studies. Furthermore, potential role for endogenous siRNAs, microRNA (miRNA) molecules, in controlling the posttranscriptional gene regulation of DMEs, DTs and NRs is discussed.

KW - Drug metabolism and transport

KW - Enzyme

KW - Gene regulation

KW - miRNA

KW - Nuclear receptor

KW - RNAi

KW - siRNA

KW - Transporter

UR - http://www.scopus.com/inward/record.url?scp=35348908290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35348908290&partnerID=8YFLogxK

U2 - 10.2174/138920007782109751

DO - 10.2174/138920007782109751

M3 - Article

VL - 8

SP - 700

EP - 708

JO - Current Drug Metabolism

JF - Current Drug Metabolism

SN - 1389-2002

IS - 7

ER -