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Photochemical Transfection: A Technology for Efficient Light-Directed Gene Delivery

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Somatic Cell and Molecular Genetics

Abstract

Most synthetic gene delivery vectors are taken up in the cell by endocytosis, and inefficient escape of the transgene from endocytic vesicles often is a major barrier for gene transfer by such vectors. To improve endosomal release we have developed a new technology, named photochemical internalization (PCI). PCI is based on photochemical reactions initiated by photosensitizing compounds localized in endocytic vesicles, inducing rupture of these vesicles upon light exposure. PCI constitutes an efficient light-inducible gene transfer method in vivo, which potentially can be developed into a site-specific method for gene delivery in in vivo gene therapy. In this paper the principle behind the PCI technology and the effect of PCI on transfection with different synthetic gene delivery vectors are reviewed. PCI treatment by the photosensitizer aluminum phthalocyanine (AlPcS2a ) strongly improves transfection mediated by cationic polymers (e.g., poly-L-lysine and polyethylenimine), while the effect on transfection with cationic lipids is more variable. The timing of the light treatment relative to the transfection period was also important, indicating that release of the DNA from early endosomes is important for the outcome of PCI-induced transfection. The possibilities of using PCI as a technology for efficient, site-specific gene delivery in in vivo gene therapy is discussed.

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Authors and Affiliations

  1. PCI Biotech AS, Hoffsvn. 48, N-0377, Oslo, Norway

    Anders Høgset

  2. Department of Biophysics, The Norwegian Radium Hospital, Montebello, N-0310, Oslo, Norway

    Anders Høgset, Lina Prasmickaite, Marit Hellum, Birgit Ø. Engesæter, Vibeke M. Olsen, Torunn E. Tjelle & Kristian Berg

  3. Department of Tumor Biology, The Norwegian Radium Hospital, Montebello, N-0310, Oslo, Norway

    Birgit Ø. Engesæter

  4. Vical Inc., 9373 Towne Centre Drive, San Diego, California, 92121

    Carl J. Wheeler

Authors
  1. Anders Høgset
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  2. Lina Prasmickaite
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  3. Marit Hellum
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  4. Birgit Ø. Engesæter
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  6. Torunn E. Tjelle
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  7. Carl J. Wheeler
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  8. Kristian Berg
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Høgset, A., Prasmickaite, L., Hellum, M. et al. Photochemical Transfection: A Technology for Efficient Light-Directed Gene Delivery. Somat Cell Mol Genet 27, 97–113 (2002). https://doi.org/10.1023/A:1022979806314

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