The concept of oligonucleotide therapeutics has constantly been evolving, and it currently is mainly consisted of small interfering RNA (siRNA), antisense oligonucleotide (ASO), microRNA (miRNA), and aptamer, activation RNA(RNAa), and ASO acting as splicing manipulators. RNA oligonucleotides acting as gRNA in gene editing, and immunomodulatory oligonucleotides are sometimes referred to also as oligonucleotide therapeutics. siRNA and ASO are the two major categories of oligonucleotide therapeutics. By recognizing and inhibiting target mRNA through complementary base pairing, siRNA and ASO can regulate the expression of corresponding proteins and thereby treat related diseases. Due to a very strong technology background and a unique international positioning strategy, Ribo's pipeline of oligonucleotide therapeutics has included siRNA, and ASO, and aptamer, with siRNA drugs as a major focus.
siRNA is a short double-stranded RNA molecule, normally with a length of 19-30 base pairs. siRNA can bind to AGO proteins to assemble into an RNA-induced silencing complex (RISC). Upon assembly of the RISC, one strand of the siRNA is degraded, while the other strand will remain associated with AGO protein and serve to recognize the messenger RNA (mRNA) of a target gene based on the complementary base pairing rule, and further induce the cleavage and degradation of the mRNA, thus blocking the expression of a target protein.
ASO is a single-stranded oligonucleotide molecule that can achieve therapeutic effect by binding to target mRNA through complementary base pairing and, either trigger further degradation of the mRNA by RNase H1 or block translation of the mRNA by steric hindrance effect, both resulting in a halt of the expression of the corresponding proteins.
Aptamer refers to the short single-stranded oligonucleotides, normally obtained through SELEX screening, that can bind to a broad range of target molecules, such as proteins, sugars. lipids, or even ions, with high affinity and specificity. Aptamer was previously translated as chemical antibody once up on a time. Up till now only one NDA of aptamer drugs was approved by US FDA.