RATIONAL DESIGN OF SEQUENCE-SPECIFIC ONCOGENE INHIBITORS BASED ON ANTISENSE AND ANTIGEN OLIGONUCLEOTIDES

Synthetic oligonucleotides can be used to control the expression of specific genes. When targeted to messenger RNAs, oligonucleotides inhibit translation (the antisense strategy). Oligonucleotides can also be targeted to specific sequences of the DNA double helix where they inhibit transcription (the antigene strategy). Both strategies can be applied to control the expression of oncogenes in tumour cells. The mRNAs of several oncogenes have been chosen as targets for antisense oligonucleotides (myc, myb, bc12, ab1, ras... ). Discrimination between the proto-oncogene and the oncogene can be achieved in the case of ras oncogenes where activation results from point mutations in the coding sequence. Regulatory sequences involved in controlling the transcription of oncogenes can also be used as targets for antigene oligonucleotides (myc, ras).