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

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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.

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Acknowledgments

This research was financially supported by grants from Ministry of Science and Technology (F104AA010002-06A0101-00210), and from the Korea Science and Engineering Foundation (KOSEF R01-2005-000-10292-0).

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Authors and Affiliations

  1. MyGene Bioscience Institute, Kangnam-gu, Seoul, South Korea

    In-Kwon Han & Woon-Won Jung

  2. College of Medicine, Pochon CHA University, Kyonggi-do, South Korea

    Mi Young Kim, Hyang-Min Byun & Tae Sun Hwang

  3. College of Medicine, Hanyang University, Seoul, South Korea

    Jung Mogg Kim

  4. College of Pharmacy, Chung-Ang University, Seoul, South Korea

    Kwang Woo Hwang

  5. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea

    Tae Gwan Park

  6. School of Life Sciences and Biotechnology, Korea University, Anam-dong, Seungbuk-gu, Seoul, South Korea

    Taehoon Chun, Gil-Jae Jeong & Yu-Kyoung Oh

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  1. In-Kwon Han
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Correspondence to Yu-Kyoung Oh.

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Han, IK., Kim, M.Y., Byun, HM. et al. Enhanced brain targeting efficiency of intranasally administered plasmid DNA: an alternative route for brain gene therapy. J Mol Med 85, 75–83 (2007). https://doi.org/10.1007/s00109-006-0114-9

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  • DOI: https://doi.org/10.1007/s00109-006-0114-9

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