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Survivin siRNA Delivery via Exosomes

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Advantages of RNA Nanoparticles for Therapy

  • Negative charge disallows nonspecific permeation of negatively charged cell membrane

  • Controlled synthesis provides defined structure and stoichiometry

  • Multi-valency allows combination therapy and simultaneous targeting and detection

  • Targeted delivery allows receptor mediated endocytosis

  • Advantageous size (10 – 40 nm)

  • Extended in vivo half-life (5-12 hr compared to 15-45 min for siRNA)

  • Avoidance of antibody induction (protein-free) allows repeated treatment for chronic diseases

  • Favorable pharmacokinetic profile in mice:
    • Half-life (T1/2) : 5-10 hr compared to 0.25-0.76 hr of siRNA counterpart;

    • Clearance (Cl): <0.13 l/kg/hr,

    • Volume of distribution (V(d)): 1.2 l/kg;

    • Does not induce interferon (IFN) response or cytokine productionï¼›

    • Repeated IV administrations of up to 30 mg/kg do not result in toxicity.

  • RNA nanoparticles are classified as chemical drugs rather than biologics. This classification facilitates drug approval.

1. Shu D, Li H, Shu Y, … Guo P. ACS Nano. 2015 Oct 27;9(10):9731-40. [link]

2. Pi F, Binzel D, Lee TJ,…Guo P. Nature Nanotechnology. 2018 Jan; 13(1):82-89. [link]

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