Nanotherapeutics for Gene Modulation that Prevents Apoptosis in the Brain and Fatal Neuroinflammation

Stopping apoptosis and neuroinflammation sounds wonderful for stroke survivors. Now if we only had a stroke leader we could ask to follow this up with translational protocols.
http://www.sciencedirect.com/science/article/pii/S1525001617305075

• Sang-Soo Kim^{1, 3},
• Antonina Rait¹,
• Emilio R. Garrido-Sanabria²,
• Kathleen F. Pirollo¹,
• Joe B. Harford³,
• Esther H. Chang^{1, ,}

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https://doi.org/10.1016/j.ymthe.2017.10.003

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Abstract

The failure of therapeutic agents to cross the blood-brain barrier (BBB) has been a major impediment in the treatment of neurological disorders and brain tumors. We have addressed this issue using an immunoliposome nanocomplex (designated scL) that delivers therapeutic nucleic acids across the BBB into the deep brain via transcytosis mediated by transferrin receptors. We validated brain delivery of payloads after systemic administration by monitoring uptake of fluorescently labeled payloads and by confirming up- or down-modulation of specific target gene expression in the brain, mainly in neuronal cells. As proof of concept for the therapeutic potential of our delivery system, we employed scL delivering an siRNA targeting tumor necrosis factor alpha to suppress neuroinflammation and neuronal apoptosis and to protect mice in lethal endotoxemia triggered by bacterial lipopolysaccharide. Brain delivery of therapeutic payloads via scL has major implications for the development of treatments for neurological disorders and brain tumors.

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Corresponding author Esther H Chang, Department of Oncology, Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, 3970 Reservoir Rd NW, TRB/E420, Washington, DC 20057-1468, USA. Phone: 202-687-8418, Fax: 202-687-8434.