A novel peptide delivers plasmids across blood-brain barrier into neuronal cells as a single-component transfer vector

PLoS One. 2013;8(3):e59642. doi: 10.1371/journal.pone.0059642. Epub 2013 Mar 29.

Abstract

There is no data up to now to show that peptide can deliver plasmid into brain as a single-component transfer vector. Here we show that a novel peptide, RDP (consisted of 39 amino acids), can be exploited as an efficient plasmid vector for brain-targeting delivery. The plasmids containing Lac Z reporter gene (pVAX-Lac Z) and BDNF gene (pVAX-BDNF) are complexed with RDP and intravenously injected into mice. The results of gel retardation assay show that RDP enables to bind DNA in a dose-dependent manner, and the X-Gal staining identity that Lac Z is specifically expressed in the brain. Also, the results of Western blot and immunofluorescence staining of BDNF indicate that pVAX-BDNF complexed with RDP can be delivered into brain, and show neuroprotective properties in experimental Parkinson's disease (PD) model. The results demonstrate that RDP enables to bind and deliver DNA into the brain, resulting in specific gene expression in the neuronal cells. This strategy provides a novel, simple and effective approach for non-viral gene therapy of brain diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blood-Brain Barrier / metabolism*
  • Brain-Derived Neurotrophic Factor / genetics
  • Drug Carriers / chemistry
  • Drug Carriers / metabolism*
  • Humans
  • Lac Operon / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Neurons / metabolism*
  • Parkinson Disease / genetics
  • Parkinson Disease / therapy
  • Peptides / chemistry
  • Peptides / metabolism*
  • Plasmids / genetics*
  • Protein Conformation

Substances

  • Brain-Derived Neurotrophic Factor
  • Drug Carriers
  • Peptides

Grants and funding

This work is supported by the grants from the Natural Science Foundation of China (31072098 and 81273416) and the Natural Science Foundation of Chongqing (CSTC 2011BB5011). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.