Antisense oligonucleotides (ASOs) are an increasingly represented class of drugs. These small sequences of nucleotides are designed to precisely target other oligonucleotides, usually RNA species, and are modified to protect them from degradation by nucleases. Their specificity is due to their sequence, so it is possible to target any RNA sequence that is already known. These molecules are very versatile and adaptable given that their sequence and chemistry can be custom manufactured. Based on the chemistry being used, their activity may significantly change and their effects on cell function and phenotypes can differ dramatically. While some will cause the target RNA to decay, others will only bind to the target and act as a steric blocker. Their incredible versatility is the key to manipulating several aspects of nucleic acid function as well as their process, and alter the transcriptome profile of a specific cell type or tissue. For example, they can be used to modify splicing or mask specific sites on a target. The entire design rather than just the sequence is essential to ensuring the specificity of the ASO to its target. Thus, it is vitally important to ensure that the complete process of drug design and testing is taken into account. ASOs’ adaptability is a considerable advantage, and over the past decades has allowed multiple new drugs to be approved. This, in turn, has had a significant and positive impact on patient lives. Given current challenges presented by the COVID-19 pandemic, it is necessary to find new therapeutic strategies that would complement the vaccination efforts being used across the globe. ASOs may be a very powerful tool that can be used to target the virus RNA and provide a therapeutic paradigm. The proof of the efficacy of ASOs as an anti-viral agent is long-standing, yet no molecule currently has FDA approval. The emergence and widespread use of RNA vaccines during this health crisis might provide an ideal opportunity to develop the first anti-viral ASOs on the market. In this review, we describe the story of ASOs, the different characteristics of their chemistry, and how their characteristics translate into research and as a clinical tool.

MiR-22 was first identified as a proto-oncogenic microRNA (miRNA) due to its ability to post-transcriptionally suppress the expression of the potent PTEN (Phosphatase And Tensin Homolog) tumor suppressor gene. miR-22 tumorigenic role in cancer was subsequently supported by its ability to positively trigger lipogenesis, anabolic metabolism, and epithelial-mesenchymal transition (EMT) towards the metastatic spread. However, during the following years, the picture was complicated by the identification of targets that support a tumor-suppressive role in certain tissues or cell types. Indeed, many papers have been published where in vitro cellular assays and in vivo immunodeficient or immunosuppressed xenograft models are used. However, here we show that all the studies performed in vivo, in immunocompetent transgenic and knock-out animal models, unanimously support a proto-oncogenic role for miR-22. Since miR-22 is actively secreted from and readily exchanged between normal and tumoral cells, a functional immune dimension at play could well represent the divider that allows reconciling these contradictory findings. In addition to a critical review of this vast literature, here we provide further proof of the oncogenic role of miR-22 through the analysis of its genomic locus vis a vis the genetic landscape of human cancer.