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Shyam R, Ren Y, Lee J, et al. Intraventricular Delivery of siRNA Nanoparticles to the Central Nervous System. Mol Ther Nucleic Acids. 2015;4:e242doi: 10.1038/mtna.2015.15.
Shyam, R., Ren, Y., Lee, J., Braunstein, K. E., Mao, H. Q., & Wong, P. C. (2015). Intraventricular Delivery of siRNA Nanoparticles to the Central Nervous System. Molecular therapy. Nucleic acids, 4e242. https://doi.org/10.1038/mtna.2015.15
Shyam, Rishab, et al. "Intraventricular Delivery of siRNA Nanoparticles to the Central Nervous System." Molecular therapy. Nucleic acids vol. 4 (2015): e242. doi: https://doi.org/10.1038/mtna.2015.15
Shyam R, Ren Y, Lee J, Braunstein KE, Mao HQ, Wong PC. Intraventricular Delivery of siRNA Nanoparticles to the Central Nervous System. Mol Ther Nucleic Acids. 2015 May 12;4:e242. doi: 10.1038/mtna.2015.15. PMID: 25965552.
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Mol Ther Nucleic Acids. 2015 May 12;4:e242. doi: 10.1038/mtna.2015.15.

Intraventricular Delivery of siRNA Nanoparticles to the Central Nervous System.

Molecular therapy. Nucleic acids

Rishab Shyam, Yong Ren, Jason Lee, Kerstin E Braunstein, Hai-Quan Mao, Philip C Wong

Affiliations

  1. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  2. 1] Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland, USA [2] Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland, USA.
  3. 1] Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA [2] Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland, USA.
  4. Department of Pathology, Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  5. 1] Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland, USA [2] Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland, USA [3] Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA [4] Whitaker Biomedical Engineering Institute, Johns Hopkins University, Baltimore, Maryland, USA.
  6. 1] Department of Pathology, Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA [2] Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

PMID: 25965552 DOI: 10.1038/mtna.2015.15

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease currently lacking effective treatment. Efficient delivery of siRNA via nanoparticles may emerge as a viable therapeutic approach to treat AD and other central nervous system disorders. We report here the use of a linear polyethyleneimine (LPEI)-g-polyethylene glycol (PEG) copolymer-based micellar nanoparticle system to deliver siRNA targeting BACE1 and APP, two therapeutic targets of AD. Using LPEI-siRNA nanoparticles against either BACE1 or APP in cultured mouse neuroblastoma (N2a) cells, we observe selective knockdown, respectively, of BACE1 or APP. The encapsulation of siRNA by LPEI-g-PEG carriers, with different grafting degrees of PEG, leads to the formation of micellar nanoparticles with distinct morphologies, including worm-like, rod-like, or spherical nanoparticles. By infusing these shaped nanoparticles into mouse lateral ventricles, we show that rod-shaped nanoparticles achieved the most efficient knockdown of BACE1 in the brain. Furthermore, such knockdown is evident in spinal cords of these treated mice. Taken together, our findings indicate that the shape of siRNA-encapsulated nanoparticles is an important determinant for their delivery and gene knockdown efficiency in the central nervous system.

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