Nonviral siRNA Delivery for Gene Silencing in Neurodegenerative Diseases

  • Satya Prakash
  • Meenakshi Malhotra
  • Venkatesh Rengaswamy
Part of the Methods in Molecular Biology book series (MIMB, volume 623)


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.

Key words

Cationic nanoparticles Targeted delivery siRNA Biotherapeutics Gene silencing Neurodegenerative diseases 



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.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Satya Prakash
    • 1
  • Meenakshi Malhotra
    • 1
  • Venkatesh Rengaswamy
    • 2
  1. 1.Biomedical Technology and Cell Therapy Research Laboratory, Departments of Biomedical Engineering and Physiology, Faculty of Medicine, Artificial Cells and Organs Research CenterMcGill UniversityMontrealCanada
  2. 2.Advance Microscopy and Imaging Facility, Molecular Virology and Cell Biology LabIndian Institute of Technology (IIT)ChennaiIndia

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