Silencing disease genes in the laboratory and the clinic

Jonathan K. Watts, David R. Corey

Research output: Contribution to journalArticle

186 Citations (Scopus)

Abstract

Synthetic nucleic acids are commonly used laboratory tools for modulating gene expression and have the potential to be widely used in the clinic. Progress towards nucleic acid drugs, however, has been slow and many challenges remain to be overcome before their full impact on patient care can be understood. Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are the two most widely used strategies for silencing gene expression. We first describe these two approaches and contrast their relative strengths and weaknesses for laboratory applications. We then review the choices faced during development of clinical candidates and the current state of clinical trials. Attitudes towards clinical development of nucleic acid silencing strategies have repeatedly swung from optimism to depression during the past 20 years. Our goal is to provide the information needed to design robust studies with oligonucleotides, making use of the strengths of each oligonucleotide technology.

Original languageEnglish (US)
Pages (from-to)365-379
Number of pages15
JournalJournal of Pathology
Volume226
Issue number2
DOIs
StatePublished - Jan 2012

Fingerprint

Gene Silencing
Nucleic Acids
Oligonucleotides
Gene Expression
Antisense Oligonucleotides
Small Interfering RNA
Patient Care
Clinical Trials
Depression
Technology
Pharmaceutical Preparations

Keywords

  • antisense oligonucleotides
  • gene silencing
  • mRNA
  • siRNA
  • therapeutics

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Silencing disease genes in the laboratory and the clinic. / Watts, Jonathan K.; Corey, David R.

In: Journal of Pathology, Vol. 226, No. 2, 01.2012, p. 365-379.

Research output: Contribution to journalArticle

Watts, Jonathan K. ; Corey, David R. / Silencing disease genes in the laboratory and the clinic. In: Journal of Pathology. 2012 ; Vol. 226, No. 2. pp. 365-379.
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