PubMed2001
Recent progress made in molecular biology, biotechnology, and genetics, especially in identifying, cloning, sequencing and characterization of normal and pathogenic genes, has led to the development of genetic therapy. Major efforts in the field can be summarized in two general approaches: gene therapy and antisense therapy. The second is to deliver to the target cells antisense molecules that target to mRNA with which they can hybridize and specifically inhibit the expression of pathogenic genes. Antisense oligonucleotides offer the possibility of specific, rational, genetic-based therapeutics. With encouraging results from preclinical and clinical studies of antisense oligonucleotides in the past decade, significant progress has been made in developing antisense therapy, with the first antisense drug now being approved for clinical use. In this article, we will discuss approaches to developing these drugs from preclinical to clinical settings. Of particular interest for the area of human cancer therapy, several cancer targets, including bcl-2, BCR-ABL, C-raf-1, Ha-ras, c-myc, PKC, PKA, p53 and MDM2, are reviewed as examples to illustrate the progress in this field and emphasize the importance of target selection and advanced antisense chemistry in the development of antisense therapy.