A photosensitising adenovirus for photodynamic therapy

Details

Serval ID
serval:BIB_4B11C128A9B8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A photosensitising adenovirus for photodynamic therapy
Journal
Gene Therapy
Author(s)
Gagnebin  J., Brunori  M., Otter  M., Juillerat-Jeanneret  L., Monnier  P., Iggo  R.
ISSN
0969-7128 (Print)
Publication state
Published
Issued date
1999
Volume
6
Number
10
Pages
1742-1750
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't
Abstract
We have developed a new approach to photodynamic therapy based on adenoviral transduction of the rate-limiting enzyme in heme synthesis. Conventional phototherapy uses porphyrin-based chemical photosensitisers, including delta-aminolaevulinic acid (ALA) which is converted to protoporphyrin IX (PpIX) by the enzymes of the heme biosynthetic pathway. The lack of a specific mechanism for targeting chemical photosensitisers and PpIX to tumour cells means that therapeutic irradiation can damage normal tissue and exposure to sunlight following treatment can cause severe burns. The rate limiting enzyme in PpIX synthesis is ALA-synthase (ALA-S). We have developed a new yeast vector system for manipulation of the adeno- virus genome and used it to construct a virus expressing a mutant form of ALA-S lacking the iron response elements which regulate ALA-S translation and the heme regulatory motifs which regulate import of ALA-S into mitochondria. The virus induces a large increase in PpIX expression and confers photosensitivity on cultured cells. Unlike conventional photodynamic therapy, a viral approach makes it possible to restrict photosensitivity by biological rather than purely physical or chemical means. As with HSV thymidine kinase, ALA-S expression is a general mechanism for sensitisation to a therapeutic agent which can easily be adapted to whatever means of gene delivery is most effective
Keywords
5-Aminolevulinate Synthetase/genetics/Adenoviridae/Amino Acid Sequence/Apoptosis/Base Sequence/Cell Line/Flow Cytometry/Gene Therapy/methods/Genetic Vectors/administration & dosage/Humans/In Situ Nick-End Labeling/Microscopy,Fluorescence/Mitochondria/metabolism/Molecular Sequence Data/Mutagenesis,Site-Directed/Photochemotherapy/Photosensitizing Agents/Skin Neoplasms/drug therapy/therapy/Tumor Cells,Cultured
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2008 18:33
Last modification date
20/08/2019 13:58
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