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Strategies for selective targeting of Auger electron emitters to tumor cells
1Department of Radiation Oncology, University of Glasgow, United Kingdom.
Unlabelled:
Strategies based on the use of Auger-emitting radionuclides require the targeting of genomic DNA. Iododeoxyuridine and its analogs, which target the process of DNA synthesis, are incorporated randomly in the genome. Alternative targeting agents are likely to assume a greater role in the future. One possibility is the use of triplex-forming oligonucleotides to target genomic DNA on a sequence-specific basis.
Methods:
A model oligonucleotide-targeting system has been developed using a synthetic DNA target sequence based on the N-myc gene. This has been used to examine the ability of alternative oligonucleotides to form DNA triplexes with homopurine-homopyrimidine tract of the target sequence.
Results:
Oligonucleotides consisting of G and A or G and T that were designed to bind in an antiparallel orientation to the homopurine strand of the target sequence formed triplexes.
Conclusion:
Triplex-forming oligonucleotides have potential as therapeutic agents for cytotoxic therapy. They may also have applications in the study of microradiobiological questions, such as the radiosensitivity of individual genes. Methods of synthesizing high specific activity triplex-forming oligonucleotides, probably using short half-life radionuclides such as 123I, are required.