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Updated: May 25, 2026

Predicting Gene Silencing Through the Spatiotemporal Control of siRNA Release from Photo-responsive Polymeric Nanocarriers
11:53

Predicting Gene Silencing Through the Spatiotemporal Control of siRNA Release from Photo-responsive Polymeric Nanocarriers

Published on: July 21, 2017

Action and reaction: the biological response to siRNA and its delivery vehicles

Rosemary L Kanasty1, Kathryn A Whitehead, Arturo J Vegas

  • 1Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.

Molecular Therapy : the Journal of the American Society of Gene Therapy
|January 19, 2012
PubMed

Insights

RNA interference (RNAi) therapeutics show promise for treating diseases, but effective delivery of small interfering RNA (siRNA) to target tissues is crucial. This review explores siRNA pharmacokinetics, pharmacodynamics, and delivery factors impacting its clinical use.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Molecular Biology

Background:

  • RNA interference (RNAi) therapeutics offer significant potential for treating various human diseases.
  • Effective delivery of RNA to target tissues is a critical challenge hindering the clinical application of RNAi-based therapies.
  • In vivo performance of short interfering RNA (siRNA) delivery formulations is influenced by multiple factors, including siRNA sequence, structure, chemical modifications, and the delivery vehicle itself.

Purpose of the Study:

  • To provide an introduction to the pharmacokinetic and pharmacodynamic principles of systemically administered siRNA and its delivery formulations.
  • To discuss factors affecting siRNA degradation, clearance, and tissue uptake.
  • To review potential immunogenicity, toxicity, and off-target effects associated with siRNA delivery.

Main Methods:

  • Literature review of pharmacokinetic and pharmacodynamic principles related to siRNA delivery.
  • Analysis of factors influencing siRNA stability, biodistribution, and cellular uptake.
  • Examination of safety considerations, including immunogenicity, toxicity, and off-target effects.

Main Results:

  • Systemic administration of siRNA is subject to degradation and rapid clearance, impacting therapeutic efficacy.
  • siRNA delivery formulations significantly influence biodistribution, tissue targeting, and cellular internalization.
  • Potential for immunogenicity, toxicity, and off-target gene silencing must be carefully evaluated for safe clinical translation.

Conclusions:

  • Understanding the pharmacokinetics and pharmacodynamics of siRNA and its delivery systems is essential for developing effective RNAi therapeutics.
  • Optimizing siRNA sequence, chemical modifications, and delivery formulations can improve in vivo performance and reduce adverse effects.
  • Addressing challenges related to degradation, clearance, immunogenicity, and toxicity is paramount for the successful clinical implementation of RNAi-based treatments.

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