Silencing disease genes in the laboratory and the clinic

Jonathan K. Watts, David R. Corey

Research output: Contribution to journalReview article

221 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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