Photochemical Internalization Enhanced Nonviral Suicide Gene Therapy
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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.
Key wordsNonviral gene transfection Cytosine deaminase gene Suicide gene therapy Photodynamic therapy Photochemical internalization Endosomal escape
This work is supported by grants from the Norwegian Radium Hospital Research Foundation. Portions of this study were made possible through access to the Laser Microbeam and Medical Program (LAMMP) at the University of California, Irvine.
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