Light-directed gene delivery by photochemical internalisation

Expert Opin Biol Ther. 2004 Sep;4(9):1403-12. doi: 10.1517/14712598.4.9.1403.


This article reviews a novel technology, named photochemical internalisation (PCI), for light-directed delivery of transgenes. Most gene therapy vectors are taken into the cell by endocytosis and, hence, are located in the endocytic vesicles. Although viral vectors have developed the means to escape from these vesicles, poor endosomal release is one of the major obstacles for non-viral vectors. PCI is a technology that allows liberation of the entrapped vectors carrying a gene in response to illumination. The method is based on chemical compounds (photosensitisers) that localise specifically in the membranes of endocytic vesicles and, following activation by light, induce the rupture of the vesicular membranes. The released transgenes can further be transferred to the nucleus, transcribed and translated. As gene liberation depends on light, enhancement of gene expression is achieved only at illuminated regions. PCI substantially improves gene transfer in vitro not only with non-viral gene vectors, but, surprisingly, also with adenoviruses and adeno-associated viruses. This article will review the background for the PCI technology and its role for gene delivery using both non-viral and viral vectors. Some aspects of the potential of PCI for site-specific gene delivery in therapeutic situations will also be discussed.

Publication types

  • Review

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Dependovirus / genetics
  • Endocytosis / radiation effects*
  • Endosomes / radiation effects*
  • Gene Expression / radiation effects
  • Gene Transfer Techniques*
  • Genes, Transgenic, Suicide
  • Genetic Vectors / administration & dosage*
  • Genetic Vectors / genetics
  • Humans
  • Indoles / administration & dosage
  • Indoles / pharmacology
  • Intracellular Membranes / chemistry
  • Intracellular Membranes / radiation effects*
  • Mice
  • Oligonucleotides, Antisense / administration & dosage
  • Organometallic Compounds / administration & dosage
  • Organometallic Compounds / pharmacology
  • Peptide Nucleic Acids / administration & dosage
  • Photochemistry
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / pharmacology*
  • Porphyrins / administration & dosage
  • Porphyrins / pharmacology
  • Singlet Oxygen / pharmacology
  • Transgenes*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • Indoles
  • Oligonucleotides, Antisense
  • Organometallic Compounds
  • Peptide Nucleic Acids
  • Photosensitizing Agents
  • Porphyrins
  • Singlet Oxygen
  • tetraphenylporphine sulfonate
  • aluminum phthalocyanine disulfonate