Antisense oligonucleotides (ASOs) are promising drugs capable of modulating the protein expression of virtually any target with high specificity and high affinity through complementary base pairing. However, this requires a deep understanding of the target sequence and significant effort in designing the correct complementary drug. In addition, ASOs have been demonstrated to be well tolerated during their clinical use. Indeed, they are already used in many diseases due to pathogenic RNAs of known sequences and in several neurodegenerative diseases and metabolic diseases, for which they were given marketing authorizations (MAs) in Europe and the United States. Their use in oncology is gaining momentum with several identified targets, promising preclinical and clinical results, and recent market authorizations in the US. However, many challenges remain for their clinical use in cancer. It seems necessary to take a step back and review our knowledge of ASOs and their therapeutic uses in oncology. The objectives of this review are (i) to summarize the current state of the art of ASOs; (ii) to discuss the therapeutic use of ASOs in cancer; and (iii) to focus on ASO usage in glioblastoma, the challenges, and the perspective ahead.

Developmental and Epileptic Encephalopathies (DEEs) represent a clinically and genetically heterogeneous group of rare and severe epilepsies. DEEs commonly begin early in infancy with frequent seizures of various types associated with intellectual disability and leading to a neurodevelopmental delay or regression. Disease-causing genomic variants have been identified in numerous genes and are implicated in over 100 types of DEEs. In this context, genes encoding voltage-gated ion channels (VGCs) play a significant role, and part of the large phenotypic variability observed in DEE patients carrying VGC mutations could be explained by the presence of genetic modifier alleles that can compensate for these mutations. This review will focus on the current knowledge of the compensatory effect of DEE-associated voltage-gated ion channels and their therapeutic implications in DEE. We will enter into detailed considerations regarding the sodium channels SCN1A, SCN2A, and SCN8A; the potassium channels KCNA1, KCNQ2, and KCNT1; and the calcium channels CACNA1A and CACNA1G.