Science

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 drug was approved by US FDA.

Efficient and specific delivery of siRNA has been the bottleneck for the therapeutic application of siRNA. The delivery systems based on the uptake of siRNA via interaction of conjugated N-acetylgalactosamine (GalNAc) with its receptor has tremendously accelerated the siRNA drug development for the treatment of diseases associated with any gene expression in hepatocytes. GalNAc-siRNA conjugates specifically bind to the asialoglycoprotein receptor (ASGPR) on the surface of hepatocytes and trigger fast endocytosis of the siRNA. This can result in highly specific and highly durable enrichment of the siRNA in hepatocytes. Based on similar principles, additional delivery technologies are under various stages of exploration at Suzhou Ribo Life Science Co., Ltd. with the strong hope for enabling robust and versatile development of siRNA drugs for diseases related to gene expression in other organs and tissues.

Suzhou Ribo Life Science Co., Ltd´s proprietary GalNAc-based System for liver TARgeting, named RIBO-GalSTAR^TM,  include a unique delivery technology for delivering oligonucleotide therapeutics for various targets and indications with origin in the liver. Ribo Life Science’s IP portfolios and the collaborations with other companies provide solid support for the product pipelines of the company and enable us to develop differentiated innovative drugs to address numerous unmet medical needs.

Suzhou Ribo Life Science Co., Ltd. has independently developed a computer software to design oligonucleotide drug sequences. Taking into consideration of sequence conservation, homology, immunogenicity and potential off-target etc. This software performs a comprehensive sequence analysis against more than 50 parameters for inter-species sequence comparison and homology assessment to rapidly select high-quality siRNA sequences with desired specificity and potential activity. Ribo has also established a platform for the high-throughput screening of oligonucleotide compounds, which are able to rapidly generate lead compounds.

Naked or unmodified oligonucleotides are highly susceptible to degradation, which associates with different degrees of their off-target effects and/or immunogenicity. Chemical modifications may affect oligonucleotide activities to various extent. Ribo scientists have systematically studied the mechanisms for siRNA degradation and correlated their potency with off-target effects. Empirical rules have been established for the chemical modifications that can significantly enhance the stability of siRNA, and lower or eliminate their off-target effects, as well as potential immunogenicity. The overall properties of our drug molecules can be greatly improved through this technology.

Based on the unique characteristics of oligonucleotides and tailored for the specific needs of drug development of oligonucleotides as new therapeutics, Suzhou Ribo Life Science Co., Ltd. has established a comprehensive platform for the CMC development of oligonucleotides and GMP manufacturing capabilities to enable the development of various types of oligonucleotide therapeutics across all developmental stages. Taking a holistic approach, Suzhou Ribo Life Science Co., Ltd. has developed manufacturing process and studied quality of oligonucleotide drug substance and product in a systematic manner, meeting the pharmaceutical needs for discovery, preclinical study, clinical trial application and clinical study.