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Nonviral siRNA Delivery for Gene Silencing in Neurodegenerative Diseases

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RNA Interference

Part of the book series: Methods in Molecular Biology ((MIMB,volume 623))

Abstract

Linking genes with the underlying mechanisms of diseases is one of the biggest challenges of genomics-driven drug discovery research. Designing an inhibitor for any neurodegenerative disease that effectively halts the pathogenicity of the disease is yet to be achieved. The challenge lies in crossing the blood-brain barrier (BBB)/blood-cerebrospinal fluid barrier (BCSFB) to reach the catalytic pockets of the enzyme/protein involved in the molecular mechanism of the disease process. Designing siRNA with exquisite specificity may result in selective suppression of the disease-linked gene. Although siRNA is the most promising method, it loses its potency in downregulating the gene due to its inherent instability, off-target effects, and lack of on-target effective delivery systems. Viral as well as nonviral delivery methods have been effectively tested in vivo for silencing of molecular targets and have resulted in significant efficacy in animal models of Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), anxiety, depression, encephalitis, glioblastoma, Huntington’s disease, neuropathic pain, and spinocerebellar ataxia. To realize the full therapeutic potential of siRNA for neurodegenerative diseases, we need to overcome many hurdles and challenges such as selecting suitable tissue-specific delivery vectors, minimizing the off-target effects, and achieving distribution in sufficient concentrations at the target tissue without any side effects. Cationic nanoparticle-mediated targeted siRNA delivery for therapeutic purposes has gained considerable clinical importance as a result of its promising efficacy.

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Acknowledgments

We gratefully acknowledge the research grant received from Canadian Institute of Health Research (CIHR) to Dr. S. Prakash. We also acknowledge support of McGill Faculty of Medicine Internal Scholarship to M. Malhotra.

Author information

Authors and Affiliations

  1. Biomedical Technology and Cell Therapy Research Laboratory, Departments of Biomedical Engineering and Physiology, Faculty of Medicine, Artificial Cells and Organs Research Center, McGill University, Montreal, QC, Canada

    Satya Prakash & Meenakshi Malhotra

  2. Advance Microscopy and Imaging Facility, Molecular Virology and Cell Biology Lab, Indian Institute of Technology (IIT), Chennai, India

    Venkatesh Rengaswamy

Authors
  1. Satya Prakash
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  2. Meenakshi Malhotra
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  3. Venkatesh Rengaswamy
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Editor information

Editors and Affiliations

  1. Dept. Surgery, Pathology & Oncology, University of Western Ontario, Windermere Road 339, London, N6A 5A5, Canada

    Wei-Ping Min

  2. MediStem Laboratories, Inc., E. Cedar Street 2027, Tempe, 85281, USA

    Thomas Ichim

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Prakash, S., Malhotra, M., Rengaswamy, V. (2010). Nonviral siRNA Delivery for Gene Silencing in Neurodegenerative Diseases. In: Min, WP., Ichim, T. (eds) RNA Interference. Methods in Molecular Biology, vol 623. Humana Press. https://doi.org/10.1007/978-1-60761-588-0_14

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  • DOI: https://doi.org/10.1007/978-1-60761-588-0_14

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60761-587-3

  • Online ISBN: 978-1-60761-588-0

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