Photochemical Internalization Enhanced Nonviral Suicide Gene Therapy

Methods Mol Biol. 2019;1895:165-176. doi: 10.1007/978-1-4939-8922-5_13.


Nonviral gene transfection overcomes some of the disadvantages of viral vectors, such as undesired immune responses, safety concerns, issues relating to bulk production, payload capacity, and quality control, but generally have low transfection efficiency. Here we describe the effects of a modified form of photodynamic therapy (PDT), i.e., photochemical internalization (PCI) to: (1) greatly increase nonviral cytosine deaminase gene (CD) transfection into tumor cells, significantly increasing the conversion of 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU), and (2) enhance the toxic efficacy of the locally produced 5-FU to induce cell death on both transfected and non-transfected bystander cells.

Keywords: Cytosine deaminase gene; Endosomal escape; Nonviral gene transfection; Photochemical internalization; Photodynamic therapy; Suicide gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / therapeutic use
  • Cell Line, Tumor
  • Cytosine Deaminase / genetics*
  • Cytosine Deaminase / metabolism
  • Flucytosine / metabolism
  • Fluorouracil / metabolism
  • Fluorouracil / therapeutic use*
  • Genes, Transgenic, Suicide*
  • Genetic Therapy / methods*
  • Glioma / drug therapy
  • Glioma / therapy
  • Neoplasms / drug therapy
  • Neoplasms / therapy*
  • Photochemotherapy / methods*
  • Prodrugs / metabolism
  • Rats


  • Antimetabolites, Antineoplastic
  • Prodrugs
  • Flucytosine
  • Cytosine Deaminase
  • Fluorouracil