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October 01, 2010 (Vol. 30, No. 17)

Expediting RNA Delivery with Small Parcels

Nanosized Particles Use Molecular Motor from Bacteriophage to Slip Into Cells and Drop Off Cargo

  • Better Delivery

    “RNA interference is regarded as one of the most important therapeutic discoveries in decades,” says Dr. Guo. However, the therapeutic relevance of small interfering RNA to silence disease-causing genes is in jeopardy unless it can be delivered in a targeted fashion. Davis calls pRNA “the missing link necessary for RNA interference to be delivered in a targeted, systemic fashion.”

    The most significant challenges in developing RNA-based therapeutics have been delivery, stability, and toxicity. To be successful, small interfering RNAs must be able to penetrate cell membranes, resist degradation by nucleases within cells, move into appropriate cell compartments, and home in on specific cells. The pRNA technology meets all these requirements without causing toxic side effects, Davis reports.

    Other companies creating RNA-based therapeutics deliver the agents to cells wrapped in liposomes or polymer structures. These formulations are large and complex, and they reportedly hinder the ability of the therapeutics to enter targeted tissues and cells. Additionally, components of the liposomes and polymers may cause toxicity or other unwanted side effects.

    In contrast, Kylin’s formulation “is made up of only RNA building blocks, so there are no additional toxicity issues,” says Davis. The nanosized particles easily enter cells and release their RNA interference cargo. “A subtle, yet important difference of Kylin’s nanoparticles,” notes Davis, “is that the pRNA is part of the therapeutic, not just a packaging and delivery system.”

    Kylin initially is focusing on pRNA-based therapeutics to treat cancer, followed by treatments for viral diseases. Among the first oncology targets is the oncogene survivin, which plays a key role in platinum-resistant ovarian cancer. “Survivin is overexpressed in most tumors, but particularly in ovarian cancer,” says Davis. Survivin, an anti-apoptotic gene, is readily targeted with appropriately designed pRNA nanoparticles. By knocking down the survivin gene, apoptosis is restored.

    Collaborating scientists at Purdue’s Bindley Bioscience Center are helping to test Kylin’s pRNA therapeutics for ovarian and other cancers. Bindley’s researchers are conducting experiments on a number of different targets in animal models with solid tumors. The collaboration “has helped us narrow down our clinical candidates and determine that ovarian cancer is our lead indication,” says Davis.

    “With pRNA, we have a unique and robust RNA interference platform, and we are actively looking for collaborations around specific therapeutic development projects with other pharmaceutical and biotechnology companies.”

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