RNA and RNA-processing enzymes

RNA and RNA-processing enzymes constitute a broad and essential class of therapeutic targets involved in the regulation of gene expression at the post-transcriptional level [2, 7]. This category includes the RNA molecules themselves—such as messenger RNA (mRNA), microRNA (miRNA), and long non-coding RNA (lncRNA)—as well as the enzymatic machinery responsible for their synthesis, splicing, modification, and degradation [4, 16]. Key enzymes in this group include RNA polymerases, spliceosomal components, RNA methyltransferases (writers), and RNases [10, 13, 19]. Targeting these molecules allows for the modulation of protein production before translation occurs, offering a way to address "undruggable" proteins by either silencing disease-causing genes or restoring the function of defective ones [7, 11, 15]. Therapeutic modalities targeting this space range from antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) to novel small molecules that can selectively bind RNA structures or modulate splicing [6, 12, 15]. While highly promising for treating genetic disorders, cancers, and viral infections, challenges such as precise tissue delivery and the avoidance of off-target effects remain central to the development of these therapies [1, 3, 18].

Other names

RNA metabolism machinery [5]RNA-binding proteins [14]RNA-modifying enzymes [19]Ribonucleoprotein complexes [4]Epitranscriptome [19]

Drugs targeting this class operate through diverse mechanisms, including splicing modulation to correct or alter exon inclusion [6, 15], RNA interference (RNAi) to induce mRNA cleavage and degradation [12, 18], and the use of antisense oligonucleotides (ASOs) for steric blocking or RNase H-mediated degradation [12]. Other approaches include inhibiting viral RNA-dependent RNA polymerases [6], inducing nonsense-mediated decay (NMD) of oncogenic transcripts [7, 15], and modulating epitranscriptomic "writer" or "eraser" enzymes to reset RNA modification patterns [19].