6. RNA therapeutics: hurdles towards clinical application
RNA-based drugs have conceptual and practical advantages compared to conventional small chemistry-based drugs or therapeutic antibodies directed against a target protein product. For example, small chemistry-based medicinal products lack absolute target speci ficity and require expensive drug screening procedures before lead compounds can be re fined towards an acceptable drug substance with su fficient speci ficity [63]. Antibodies can only recognize targets that are both druggable and secreted or extracellular, because there is no good strategy to deliver them inside cells [64]. By contrast, siRNAs and ASOs can in principle suppress any gene, even if it is highly expressed, including non-coding genes, which conventional chemical therapeutics or antibodies cannot [7]. Unlike antibodies, RNAs can be chemically synthesized, thus leading to cheaper and more easily manufactured drugs than biologics, which can su ffer from batch-to-batch variability. Antibodies need to be administered every few weeks, and patients often develop immunological responses, which can limit the e ffectiveness of antibody therapy with continued use. Thus far, there is no evidence of adaptive immune responses against RNA therapeutics [65]. A final potential advantage of RNA drugs that utilize a Watson-Crick targetbinding motif, compared to antibodies, is that an antisense oligo is straightforward to design using the complementary sequence to speci- fically bind and inactivate the target sequence, being either a mRNA, a ncRNA or a ssDNA [7,65] .
