Genetic association meets RNA interference: Large-scale genomic screens for causation and mechanism of complex diseases

Mitchell Martin, John F. Reidhaar-Olson, Cristina M. Rondinone

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

While the genomic era offers great promise for biomedicine in general and for biomarker discovery in particular, it has yet to significantly impact drug target discovery. Meanwhile, despite improvements over the past 20 years in reducing attrition in clinical trials due to adverse drug responses, the pharmaceutical industry continues to be beset by the high rate of attrition of compounds in late-stage development, primarily due to the lack of drug efficacy. Clearly, even highly potent drugs with ideal safety and pharmacokinetic profiles will fail to survive clinical trials if the drug target itself is not a key point of intervention for most patients. Genetic association studies and RNA interference are two scaleable genomic approaches that together can address the quality as well as quantity of candidate drug targets. Human genetic information has long been used to identify 'molecular bottlenecks' that can highlight the importance of a gene or pathway at the clinical level. The recent availability of the human HapMap and of high-throughput genotyping platforms now enables more systematic genetic screens for novel, clinically-relevant drug targets. In addition, RNA interference can help dissect the molecular role of a candidate drug target in preclinical model systems in vitro and in vivo. Wider applicability of RNA interference methods will closely follow continued progress on efficient delivery into appropriate cell models and target tissues.

Original languageEnglish (US)
Pages (from-to)455-464
Number of pages10
JournalPharmacogenomics
Volume8
Issue number5
DOIs
StatePublished - May 2007
Externally publishedYes

Fingerprint

RNA Interference
Causality
Pharmaceutical Preparations
Clinical Trials
HapMap Project
Critical Pathways
Medical Genetics
Drug Industry
Genetic Association Studies
Drug Discovery
Pharmacokinetics
Biomarkers
Safety
Genes

Keywords

  • Drug target
  • Genotype
  • Haplotype
  • Pharmacogenetics
  • Pharmacogenomics
  • RNA interference
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Pharmacology
  • Genetics(clinical)

Cite this

Genetic association meets RNA interference : Large-scale genomic screens for causation and mechanism of complex diseases. / Martin, Mitchell; Reidhaar-Olson, John F.; Rondinone, Cristina M.

In: Pharmacogenomics, Vol. 8, No. 5, 05.2007, p. 455-464.

Research output: Contribution to journalArticle

Martin, Mitchell ; Reidhaar-Olson, John F. ; Rondinone, Cristina M. / Genetic association meets RNA interference : Large-scale genomic screens for causation and mechanism of complex diseases. In: Pharmacogenomics. 2007 ; Vol. 8, No. 5. pp. 455-464.
@article{11ef320629e04bb682be53ccb86a2a1c,
title = "Genetic association meets RNA interference: Large-scale genomic screens for causation and mechanism of complex diseases",
abstract = "While the genomic era offers great promise for biomedicine in general and for biomarker discovery in particular, it has yet to significantly impact drug target discovery. Meanwhile, despite improvements over the past 20 years in reducing attrition in clinical trials due to adverse drug responses, the pharmaceutical industry continues to be beset by the high rate of attrition of compounds in late-stage development, primarily due to the lack of drug efficacy. Clearly, even highly potent drugs with ideal safety and pharmacokinetic profiles will fail to survive clinical trials if the drug target itself is not a key point of intervention for most patients. Genetic association studies and RNA interference are two scaleable genomic approaches that together can address the quality as well as quantity of candidate drug targets. Human genetic information has long been used to identify 'molecular bottlenecks' that can highlight the importance of a gene or pathway at the clinical level. The recent availability of the human HapMap and of high-throughput genotyping platforms now enables more systematic genetic screens for novel, clinically-relevant drug targets. In addition, RNA interference can help dissect the molecular role of a candidate drug target in preclinical model systems in vitro and in vivo. Wider applicability of RNA interference methods will closely follow continued progress on efficient delivery into appropriate cell models and target tissues.",
keywords = "Drug target, Genotype, Haplotype, Pharmacogenetics, Pharmacogenomics, RNA interference, Single nucleotide polymorphism",
author = "Mitchell Martin and Reidhaar-Olson, {John F.} and Rondinone, {Cristina M.}",
year = "2007",
month = "5",
doi = "10.2217/14622416.8.5.455",
language = "English (US)",
volume = "8",
pages = "455--464",
journal = "Pharmacogenomics",
issn = "1462-2416",
publisher = "Future Medicine Ltd.",
number = "5",

}

TY - JOUR

T1 - Genetic association meets RNA interference

T2 - Large-scale genomic screens for causation and mechanism of complex diseases

AU - Martin, Mitchell

AU - Reidhaar-Olson, John F.

AU - Rondinone, Cristina M.

PY - 2007/5

Y1 - 2007/5

N2 - While the genomic era offers great promise for biomedicine in general and for biomarker discovery in particular, it has yet to significantly impact drug target discovery. Meanwhile, despite improvements over the past 20 years in reducing attrition in clinical trials due to adverse drug responses, the pharmaceutical industry continues to be beset by the high rate of attrition of compounds in late-stage development, primarily due to the lack of drug efficacy. Clearly, even highly potent drugs with ideal safety and pharmacokinetic profiles will fail to survive clinical trials if the drug target itself is not a key point of intervention for most patients. Genetic association studies and RNA interference are two scaleable genomic approaches that together can address the quality as well as quantity of candidate drug targets. Human genetic information has long been used to identify 'molecular bottlenecks' that can highlight the importance of a gene or pathway at the clinical level. The recent availability of the human HapMap and of high-throughput genotyping platforms now enables more systematic genetic screens for novel, clinically-relevant drug targets. In addition, RNA interference can help dissect the molecular role of a candidate drug target in preclinical model systems in vitro and in vivo. Wider applicability of RNA interference methods will closely follow continued progress on efficient delivery into appropriate cell models and target tissues.

AB - While the genomic era offers great promise for biomedicine in general and for biomarker discovery in particular, it has yet to significantly impact drug target discovery. Meanwhile, despite improvements over the past 20 years in reducing attrition in clinical trials due to adverse drug responses, the pharmaceutical industry continues to be beset by the high rate of attrition of compounds in late-stage development, primarily due to the lack of drug efficacy. Clearly, even highly potent drugs with ideal safety and pharmacokinetic profiles will fail to survive clinical trials if the drug target itself is not a key point of intervention for most patients. Genetic association studies and RNA interference are two scaleable genomic approaches that together can address the quality as well as quantity of candidate drug targets. Human genetic information has long been used to identify 'molecular bottlenecks' that can highlight the importance of a gene or pathway at the clinical level. The recent availability of the human HapMap and of high-throughput genotyping platforms now enables more systematic genetic screens for novel, clinically-relevant drug targets. In addition, RNA interference can help dissect the molecular role of a candidate drug target in preclinical model systems in vitro and in vivo. Wider applicability of RNA interference methods will closely follow continued progress on efficient delivery into appropriate cell models and target tissues.

KW - Drug target

KW - Genotype

KW - Haplotype

KW - Pharmacogenetics

KW - Pharmacogenomics

KW - RNA interference

KW - Single nucleotide polymorphism

UR - http://www.scopus.com/inward/record.url?scp=34248515265&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34248515265&partnerID=8YFLogxK

U2 - 10.2217/14622416.8.5.455

DO - 10.2217/14622416.8.5.455

M3 - Article

C2 - 17465709

AN - SCOPUS:34248515265

VL - 8

SP - 455

EP - 464

JO - Pharmacogenomics

JF - Pharmacogenomics

SN - 1462-2416

IS - 5

ER -