Preclinical and clinical development of siRNA-based therapeutics

Adv Drug Deliv Rev. 2015 Jun 29;87:108-19. doi: 10.1016/j.addr.2015.01.007. Epub 2015 Feb 7.


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.

Keywords: EphA2; Gene silencing; Nanocarriers; Nanoliposomes; Ovarian cancer; Therapeutic use; siRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Drug Carriers / chemistry
  • Drug Design
  • Drug Evaluation, Preclinical
  • Female
  • Gene Targeting
  • Humans
  • Nanoparticles / chemistry
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • RNA Interference / drug effects*
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / adverse effects
  • RNA, Small Interfering / pharmacokinetics
  • RNA, Small Interfering / therapeutic use*
  • Receptor, EphA2 / genetics*


  • Drug Carriers
  • RNA, Small Interfering
  • Receptor, EphA2