Preclinical and clinical development of siRNA-based therapeutics

Gulnihal Ozcan, Bulent Ozpolat, Robert L. Coleman, Anil K. Sood, Gabriel Lopez-Berestein

Research output: Contribution to journalReview articlepeer-review

331 Scopus citations

Abstract

The discovery of RNA interference, first in plants and Caenorhabditis elegans and later in mammalian cells, led to the emergence of a transformative view in biomedical research. Knowledge of the multiple actions of non-coding RNAs has truly allowed viewing DNA, RNA and proteins in novel ways. Small interfering RNAs (siRNAs) can be used as tools to study single gene function both in vitro and in vivo and are an attractive new class of therapeutics, especially against undruggable targets for the treatment of cancer and other diseases. Despite the potential of siRNAs in cancer therapy, many challenges remain, including rapid degradation, poor cellular uptake and off-target effects. Rational design strategies, selection algorithms, chemical modifications and nanocarriers offer significant opportunities to overcome these challenges. Here, we review the development of siRNAs as therapeutic agents from early design to clinical trial, with special emphasis on the development of EphA2-targeting siRNAs for ovarian cancer treatment.

Original languageEnglish (US)
Pages (from-to)108-119
Number of pages12
JournalAdvanced Drug Delivery Reviews
Volume87
DOIs
StatePublished - Jun 29 2015

Keywords

  • EphA2
  • Gene silencing
  • Nanocarriers
  • Nanoliposomes
  • Ovarian cancer
  • SiRNA
  • Therapeutic use

ASJC Scopus subject areas

  • Pharmaceutical Science

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