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Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer

Nature Materials volume 4, pages 934–941 (2005)Cite this article

Abstract

The control of gene transfection in the body is a core issue in gene therapy. Photochemical internalization is a technology that allows light-induced delivery of DNA, drugs or other biological factors directly inside cells. Usually it requires that a photosensitizer be added to the drug-delivery system to photochemically destabilize the endosomal membrane. Here we present a system for in vivo DNA delivery in which these two components are assembled into one structure. This is a ternary complex composed of a core containing DNA packaged with cationic peptides and enveloped in the anionic dendrimer phthalocyanine, which provides the photosensitizing action. The ternary complex showed more than 100-fold photochemical enhancement of transgene expression in vitro with reduced photocytotoxicity. In an animal experiment, subconjuctival injection of the ternary complex followed by laser irradiation resulted in transgene expression only in the laser-irradiated site. This work demonstrates a new biomedical application for dendrimers, and the first success in the photochemical-internalization-mediated gene delivery in vivo.

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Figure 1: Preparation and characterization of the ternary complex.
Figure 2: Properties of DPc and the pDNA/CP4/DPc ternary complexes.
Figure 3: In vitro tranfection efficiency and cytotoxicity to HeLa cells.
Figure 4: Transfection to the conjunctival tissue to rat eyes.
Figure 5: A scheme for itinerary of the ternary complex to the transgene expression.

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Acknowledgements

We thank N. Kanayama (the University of Tokyo), S. Kawauchi (National Defense Medical College) and K. Date (the University of Tokyo) for technical assistance. This work was supported in part by the Core Research Program for Evolutional Science and Technology (CREST) from Japan Science and Technology Agency (JST).

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  1. Nobuhiro Nishiyama and Aya Iriyama: These authors contributed equally to this paper

Authors and Affiliations

  1. Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Nobuhiro Nishiyama, Keiji Itaka & Kazunori Kataoka

  2. Department of Ophthalmology, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Aya Iriyama, Yuji Inoue, Hidenori Takahashi, Yasuo Yanagi & Yasuhiro Tamaki

  3. Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan

    Woo-Dong Jang, Kanjiro Miyata & Kazunori Kataoka

  4. Department of Clinical Vascular Regeneration, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Hiroyuki Koyama

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  1. Nobuhiro Nishiyama
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Correspondence to Kazunori Kataoka.

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Supplementary information

Supplementary Information

Supplementary methods and data, supplementary table S1 and figures S1, S2, S3 and S4 (PDF 482 kb)

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Nishiyama, N., Iriyama, A., Jang, WD. et al. Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer. Nature Mater 4, 934–941 (2005). https://doi.org/10.1038/nmat1524

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