RNA-based and RNA-targeted therapeutics

RNA and oligonucleotide therapeutics as well as small molecule drugs designed to target human RNA in the body in order to treat medical conditions. RNA-targeted therapeutics may target protein coding RNA molecules or non-coding regulatory RNA molecules.

RNA therapeutics include RNA molecules that encode proteins, RNA molecules that target nucleic acids (either DNA or RNA) and RNA molecules that target proteins. Those that target nucleic acids include single-stranded antisense oligonucleotides (ASOs) and double-stranded molecules known to operate through the RNA interference (RNAi) pathway. RNA therapeutics that target proteins are called RNA aptamers.

ASOs are short stretches or modified DNA of 13-25 nucleotides which act by preventing mRNA from being translated into protein through blocking start of translation or tagging mRNA for degradation. An ASO may alter mRNA splicing, a maturation process necessary for translation to occur. RNAi based therapies use double-stranded molecules of small interfering RNAs (siRNAs) of 21-23 nucleotides or microRNAs, which prevent protein translation through degradation of mRNA. Double stranded molecules used in RNAi based therapies are more difficult to gain entry into cells compared with single stranded ASOs.

RNA aptamers are designed to bind a specific site on a specific protein to affect its function. RNA aptamers have rapid action and reversibility.

Messenger RNA (mRNA) are the RNA molecules that code for proteins. After gene transcription , coding RNAs undergo processing steps such as splicing before forming a mature mRNA molecules . Some noncoding RNAs (ncRNAs) perform enzymatic catalysis during splicing and translation and others regulate gene expression. Small ncRNA (sncRNA), also called small RNA (sRNA) includes microRNA (miRNA) which can suppress translation, degrade mRNA and silence gene loci through epigenetics. sncRNA have been discovered that originate from small nucleolar RNA (snoRNA), tRNA and rRNA and act as miRNA or modulate cellular processes like ribosome biogenesis. Long ncRNA (lncRNA) are more than 200 nucleotides long and function in regulating gene expression in the nucleus at the level of transcription and epigenetics or in the cytosol control mRNA turnover and regulation. Expression of ncRNAs is tissue-specific as they regulate development and physiology. Illnesses such as cardiovascular disease, diabetes, neuronal degenerative disease and cancer have shown abnormal expression of miRNAs and lncRNAs.