Enhanced brain targeting efficiency of intranasally administered plasmid DNA: An alternative route for brain gene therapy

In Kwon Han, Mi Young Kim, Hyang Min Byun, Tae Sun Hwang, Jung Mogg Kim, Kwang Woo Hwang, Tae Gwan Park, Woon Won Jung, Taehoon Chun, Gil Jae Jeong, Yu Kyoung Oh

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Recently, nasal administration has been studied as a noninvasive route for delivery of plasmid DNA encoding therapeutic or antigenic genes. Here, we examined the brain targeting efficiency and transport pathways of intranasally administered plasmid DNA. Quantitative polymerase chain reaction (PCR) measurements of plasmid DNA in blood and brain tissues revealed that intranasally administered pCMVβ (7.2 kb) and pN2/CMVβ (14.1 kb) showed systemic absorption and brain distribution. Following intranasal administration, the β-galactosidase protein encoded by these plasmids was significantly expressed in brain tissues. Kinetic studies showed that intranasally administered plasmid DNA reached the brain with a 2,595-fold higher efficiency than intravenously administered plasmid DNA did, 10 min post-dose. Over 1 h post-dose, the brain targeting efficiencies were consistently higher for intranasally administered plasmid DNA than for intravenously administered DNA. To examine how plasmid DNA enters the brain and moves to the various regions, we examined tissues from nine brain regions, at 5 and 10 min after intranasal or intravenous administration of plasmid DNA. Intravenously administered plasmid DNA displayed similar levels of plasmid DNA in the nine different regions, whereas, intranasally administered plasmid DNA exhibited different levels of distribution among the regions, with the highest plasmid DNA levels in the olfactory bulb. Moreover, plasmid DNA was mainly detected in the endothelial cells, but not in glial cells. Our results suggest that intranasally applied plasmid DNA may reach the brain through a direct route, possibly via the olfactory bulb, and that the nasal route might be an alternative method for efficiently delivering plasmid DNA to the brain.

Original languageEnglish
Pages (from-to)75-83
Number of pages9
JournalJournal of Molecular Medicine
Volume85
Issue number1
DOIs
Publication statusPublished - 2007 Jan

Keywords

  • Biodistribution
  • Brain gene delivery
  • Gene expression
  • Nasal route

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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    Han, I. K., Kim, M. Y., Byun, H. M., Hwang, T. S., Kim, J. M., Hwang, K. W., Park, T. G., Jung, W. W., Chun, T., Jeong, G. J., & Oh, Y. K. (2007). Enhanced brain targeting efficiency of intranasally administered plasmid DNA: An alternative route for brain gene therapy. Journal of Molecular Medicine, 85(1), 75-83. https://doi.org/10.1007/s00109-006-0114-9