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SiRNA delivery with exosome nanoparticles

Nature Biotechnology volume 29, pages 325–326 (2011)Cite this article

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A natural system for ferrying RNA between cells is used to transport siRNA to the mouse brain.

Research on therapeutic RNAi has focused on three classes of delivery vehicle: viruses, polycationic polyethylenimine (PEI)-based nanoparticles and liposomes. All three have shown some successes, especially in inducing RNAi in the liver. Nonetheless the broad goal of achieving clinically efficient gene silencing in the desired target tissue, while avoiding immune activation and toxicity, is still far out of reach. Viruses can mediate long-term gene silencing by integrating small hairpin RNA expression cassettes into the genome and can be engineered for specific tissue tropism, but they have major drawbacks (Fig. 1b). Viruses can be cleared in the bloodstream by preexisting antibodies and can activate complement or coagulation factors2. They can also induce neutralizing antibody responses that prevent repeated administration. Dysregulation of gene expression in the target cell by insertional mutagenesis is a major safety issue, and some viruses integrate only in dividing cells.

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Figure 1: Advantages and drawbacks of siRNA delivery by exosomes, viruses, lipid nanoparticles or polymeric nanoparticles.

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Affiliations

  1. Jasper G. van den Boorn, Martin Schlee, Christoph Coch and Gunther Hartmann are at the Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.

    Jasper G van den Boorn, Martin Schlee, Christoph Coch & Gunther Hartmann

Authors
  1. Jasper G van den Boorn
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  2. Martin Schlee
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  3. Christoph Coch
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  4. Gunther Hartmann
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Correspondence to Gunther Hartmann.

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The authors declare no competing financial interests.

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van den Boorn, J., Schlee, M., Coch, C. et al. SiRNA delivery with exosome nanoparticles. Nat Biotechnol 29, 325–326 (2011). https://doi.org/10.1038/nbt.1830

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