Antisense: Oligonucleotides

The use of oligonucleotides as discriminating inhibitors of gene expression offers a novel approach to this treatment of cancer cell growth. In the antisense approach, oligonucleotides complementary to specific sequences target the mRNA involved in the development in important cellular functions and protein production. The therapeutic application of the antisense approach is currently under exploration in many different fields including oncology and immunology. Nuclease degradation is a major limitation for the use of phosphodiester oligonucleotides as therapeutic agents, due to the unforeseen need for production on a large scale and lack of adequate vectors.

Antisense:
Antisense oligonucleotide defined as the oligodeoxyribonucleotide (oDNA) sequence that is complementary to the DNA or RNA sequence of the target gene. Antisense RNA defined as the antisense cDNA, which is complementary to the RNA sequence of the gene.

• A design of antisense can recognize precise DNA location in a gene
• Antisense can be equipped to recognize a single mRNA species among a myriad of mRNAs
• Antisense can discriminate between the genetic information of normal and mutated oncogenes in breast cancer cells.

The strategy behind anti­sense therapy is the development of specific therapeutic agents that aim to correct the mutations and abnormal expression of cellular genes in breast tumor cells by decreasing gene expression, inducing degradation of target mRNA and causing premature termination of transcription. Many in vitro and in vivo studies have investigated the therapeutic efficacy of oligonucle­ otides and antisense RNAs. These studies have demonstrated specific inhibi­ tion of tumor cell growth by antisense therapy and have shown synergistic inhibitory effects between antisense oligonucleotides or antisense RNA and conventional chemotherapeutic drugs used in the treatment of breast can­cer. Antisense oligonucleotides with modifications will improve their ability to penetrate cells, bind to gene sequences and disrupt target gene function. Many delivery systems for antisense RNA and antisense oligonucle­otides have been developed, including virus vectors (retrovirus, adenovirus and adeno-associate virus) and liposomes, to carry the antisense RNA or oli­gonucleotides through the cell membrane into the cytoplasm and nucleus of the tumor cells. Various studies showed that antisense therapies directed at abnormal genes in breast cancer are potentially useful in the treat­ment of breast cancer. Antisense thera­peutic strategies are under development and provide a basis for a better understanding of the mechanisms of gene regulation and growth inhibition in human breast can­cer. The ability to benefit from these characteristics presents a unique opportunity in treating all cancers.

The growth potential of the mass production of antisense will bring a new modification to viral vectors, which will aim at reducing toxicity, increasing immunogenic condition, and improving the regulation of gene expression.