Intranasal delivery of hGDNF plasmid DNA nanoparticles results in long-term and widespread transfection of perivascular cells in rat brain

Amirah E.E. Aly, Brendan Harmon, Linas Padegimas, Ozge Sesenoglu-Laird, Mark J. Cooper, David M. Yurek, Barbara L. Waszczak

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The intranasal route of administration allows large therapeutics to circumvent the blood–brain barrier and be delivered directly to the CNS. Here we examined the distribution and pattern of cellular transfection, and the time course of transgene expression, in the rat brain after intranasal delivery of plasmid DNA nanoparticles (NPs) encoding hGDNF fused with eGFP. Intranasal administration of these NPs resulted in transfection and transgene expression throughout the rat brain, as indicated by eGFP ELISA and eGFP-positive cell counts. Most of the transfected cells were abluminal and immediately adjacent to capillaries and are likely pericytes, consistent with their distribution by perivascular transport. Intranasal administration of these plasmid DNA NPs resulted in significant, long-term transgene expression in rat brain, with highest levels at 1 week and continued expression for 6 months. These results provide evidence in support of intranasal DNA NPs as a non-invasive, long-term gene therapy approach for various CNS disorders.

Original languageEnglish
Pages (from-to)20-33
Number of pages14
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume16
DOIs
StatePublished - Feb 2019

Bibliographical note

Funding Information:
Support: This research was supported in part by the Michael J. Fox Foundation for Parkinson's Research , a Northeastern University Tier 1 grant (BLW), and National Institutes of Health R01NS75871 (DMY).

Publisher Copyright:
© 2018 Elsevier Inc.

Keywords

  • GDNF
  • Gene therapy
  • Intranasal
  • Nanoparticles
  • Pericytes

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science (all)
  • Pharmaceutical Science

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