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Preparation of Exosomes for siRNA Delivery to Cancer Cells
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A ribonucleoprotein octamer for targeted siRNA delivery

Wanyi Tai1, Junwei Li1, Eva Corey2

  • 1Department of Bioengineering, University of Washington, Seattle, WA, USA.

Nature Biomedical Engineering
|April 3, 2019
PubMed

Insights

Researchers developed a novel nanoparticle for targeted delivery of small interfering RNA (siRNA) to cancer cells. This breakthrough overcomes challenges in RNA interference therapy, enabling precise gene silencing in prostate cancer models.

Area of Science:

  • Biotechnology
  • Nanomedicine
  • Molecular Biology

Background:

  • Cell-specific delivery of small interfering RNA (siRNA) for RNA interference (RNAi) therapies faces significant hurdles in clinical translation.
  • Existing delivery vehicles often present conflicting properties, such as facilitating endosomal escape but compromising in vivo targeting and stability.

Purpose of the Study:

  • To engineer a novel nanoparticle for efficient and targeted in vivo delivery of siRNA.
  • To overcome the limitations of current delivery systems for RNAi therapeutics.

Main Methods:

  • Development of a self-assembled, biocompatible ribonucleoprotein-octamer nanoparticle (~30 nm).
  • Incorporation of a poly(ethylene glycol) scaffold, an endosomolytic peptide, and a double-stranded RNA-binding domain.
  • Functionalization with a targeting ligand for prostate-specific membrane antigen (PSMA).

Main Results:

  • The nanoparticle demonstrated efficient siRNA loading (>30 wt%) and endosomal destabilization.
  • Targeted gene silencing of polo-like kinase 1 (PLK1) was achieved in prostate cancer cells in vitro.
  • Effective in vivo gene silencing was observed in mouse models of prostate cancer following intravenous injection.

Conclusions:

  • The developed ribonucleoprotein-octamer nanoparticle is a versatile nanocarrier for intracellularly acting biologics.
  • This platform offers a promising strategy for advancing RNAi-based therapies towards clinical application.

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