Long-term transgene expression in the central nervous system using DNA nanoparticles

David M. Yurek, Anita M. Fletcher, George M. Smith, Kim B. Seroogy, Assem G. Ziady, Joseph Molter, Tomasz H. Kowalczyk, Linas Padegimas, Mark J. Cooper

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


This study demonstrates proof of concept for delivery and expression of compacted plasmid DNA in the central nervous system. Plasmid DNA was compacted with polyethylene glycol substituted lysine 30-mer peptides, forming rod-like nanoparticles with diameters between 8 and 11 nm. Here we show that an intracerebral injection of compacted DNA can transfect both neurons and glia, and can produce transgene expression in the striatum for up to 8 weeks, which was at least 100-fold greater than intracerebral injections of naked DNA plasmids. Bioluminescent imaging (BLI) of injected animals at the 11th postinjection week revealed significantly higher transgene activity in animals receiving compacted DNA plasmids when compared to animals receiving naked DNA. There was minimal evidence of brain inflammation. Intrastriatal injections of a compacted plasmid encoding for glial cell line-derived neurotrophic factor (pGDNF) resulted in a significant overexpression of GDNF protein in the striatum 1-3 weeks after injection.

Original languageEnglish
Pages (from-to)641-650
Number of pages10
JournalMolecular Therapy
Issue number4
StatePublished - 2009

Bibliographical note

Funding Information:
This research was supported in part by NS50311 (D.M.Y.), NS040592 (G.M.S.), the Michael J. Fox Foundation for Parkinson’s Research (D.M.Y., M.J.C.), the Jelm Foundation (D.M.Y.), and the State of Ohio Biomedical Research and Technology Transfer fund (A.G.Z., M.J.C.). The authors thank Kerstin Lundgren for her excellent technical assistance.

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery


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