Résumé
Antisense oligonucleotides (ASOs) have been used as therapeutic tools in the treatment of numerous rare genetic diseases for many years. They enable RNAs to be targeted to modulate their expression or modify their splicing so that the patient expresses a corrected protein. ASOs thus offer the possibility of targeting upstream of the protein, which is not always a possible target for conventional drugs. Numerous mechanisms of cancer development and resistance to its treatment are known and studied, but these identified targets are not always accessible by conventional drugs. Thus, the use of therapeutic ASOs as anticancer drugs is very attractive, and numerous pre-clinical experiments have demonstrated their efficacy on cancer cells, both in vitro and in vivo. Clinical trials of ASOs as cancer treatments have multiplied. However, in 30 years, no ASO has been able to achieve sufficient clinical results in humans to be marketed: in addition to recurring adverse effects, it is above all the lack of efficacy that is noteworthy. The aim of this thesis is therefore to present ASOs, their mode of action and the parameters to be taken into account when designing them, the results obtained in the treatment of rare diseases, and then to examine the reasons for their ineffectiveness in oncology.