The Use of Synthetic Oligonucleotides as Protein Inhibitors and Anticode Drugs in Cancer Therapy: Accomplishments and Limitations

Title: The Use of Synthetic Oligonucleotides as Protein Inhibitors and Anticode Drugs in Cancer Therapy: Accomplishments and Limitations

Volume: 2 Issue: 4

Author(s): Marcella Faria and Henning Ulrich

Affiliation:

Keywords: Synthetic Oligonucleotides, Accomplishments, Protein Inhibitors, phosphoramidite, Peptide nucleic acid, Triplex-forming molecules, Triple-helix forming oligonucleotides, Polymerase chain reaction

Abstract: The function of gene products can be altered at many levels, including the mutation of gene sequence and the change in steady state levels of mRNA and / or protein by various mechanisms. The cumulative malfunction of specific gene products underlies many pathological conditions such as the multi-step and multi-cause acquisition of cancer. Here we discuss two oligonucleotide-based strategies in which these compounds target defective gene products acting either as antiprotein or anticode agents. The SELEX technique (systematic evolution of ligands by exponential enrichment) is an antiprotein approach in which nuclease-resistant DNA or RNA aptamers are selected by their ability to bind their protein targets with high affinity and specificity of the same range as antibodies. Such inhibitors were previously evolved against a great variety of targets, including receptors, growth factors and adhesion molecules implicated in the genesis of some kinds of cancer. Moreover, some results have already been obtained in animal models. The antigene technology interferes with earlier steps in the information flow leading from gene to protein. In this approach selective gene silencing is provided by the formation of stable and specific complexes between triplex forming molecules and their DNA targets. The feasibility of this strategy as well as a molecular mechanism for the action of antigene oligonucleotides has been demonstrated in cellular systems and in vivo. The use of oligonucleotide drugs (of either the antiprotein or the anticode type) as a viable approach to cancer therapy is limited by some common problems that will be discussed.

Cite this article as:

Faria Marcella and Ulrich Henning, The Use of Synthetic Oligonucleotides as Protein Inhibitors and Anticode Drugs in Cancer Therapy: Accomplishments and Limitations, Current Cancer Drug Targets 2002; 2 (4) . https://dx.doi.org/10.2174/1568009023333827