siRNA Therapeutics Development
In recent years, multiple researches have demonstrated the tremendous potential of RNA interference (RNAi) drugs targeting disease-causing genes to treat diseases that have plagued humans for years. Harnessing the power of RNAi, our company is committed to providing customers with specially designed small interfering RNAs (siRNAs) to knock down the expression of target genes in a sequence-specific manner. Our ability to synthesize siRNAs combined with our experience in RNA therapy development opens up the possibility of addressing a wide range of rare diseases.
Background
RNA interference (RNAi) is a phenomenon that inhibits the expression of specific genes in normal organisms. When a double-stranded RNA (dsRNA) homologous to the coding region of an endogenous mRNA is introduced into a cell, the mRNA is degraded and gene expression is silenced. SiRNA-mediated RNAi-induced gene silencing is an important form of gene expression regulation in living organisms. Compared to chemical drugs or antibodies, siRNA has an inherent advantage. By selecting the correct nucleotide sequence for targeting mRNA, it is possible to target many targets that are "undruggable" by small molecules and antibodies, such as AAT, APOC3, HTT, and DMPK. Moreover, siRNAs are far less time-consuming to screen and develop than chemical and antibody drugs.
siRNA-based therapeutics have been developed for more than 20 years and have achieved great success. Several siRNA-based therapies have been approved by the FDA for the treatment of rare metabolic diseases. For example, patisiran for hereditary transthyretin amyloidosis (hATTR), givosiran for acute hepatic porphyria (AHP), and lumasiran for primary hyperoxaluria type 1 (PH1). In addition, siRNA-based therapies for many other rare diseases are currently being evaluated.
Fig. 1 Examples of siRNA drugs. (Kim Y K, et al., 2022)
Our Services
To improve the therapeutic efficacy of siRNA-based therapies and reduce the side effects of siRNA, our researchers work to offer customers a variety of chemical modifications of siRNA and multiple delivery systems. We have studied a range of modification modalities and evaluated their impact on activity, specificity, stability, and biosafety in preclinical settings. We provide not only general siRNA and various modified and labeled siRNA products, but also customized modified siRNA products.
- siRNA synthesis
We have advanced core technology in siRNA synthesis and can synthesize high-quality siRNA according to customers' requirements. Our siRNA products use the optimized solid phase synthesis process and HPLC purification process to ensure stable quality. - siRNA modification
We offer our customers a variety of chemical modifications to improve the specificity, stability, and efficacy of siRNA.
Phosphonate modification
We provide various chemical modifications of siRNA phosphate backbone, such as phosphorodithioate modified siRNAs (PS2-siRNA), isolated amide-linked siRNAs, and phosphorothioate siRNAs (PS-siRNAs).
Ribose modification
We provide various chemical modifications of siRNA ribose, such as D- or L-Isonucleoside (isoNA) modified siRNAs, 2'-O-GP modified siRNAs (GP-siRNAs), 2'-Azido RNA (2'-N3 Cytidine & 2'-N3 guanosine), and trivalent N-acetylgalactosamine conjugated siRNAs (siRNA-GalNAc conjugate).
Nucleobase and sugar modifications
We provide chemical modifications of siRNA nucleobase and ribose sugar, such as 5-fluoro-2'-deoxyuridine modified siRNA, 2'-OMe-phosphorodithioate modified siRNAs, and C-5 PLA-substituted pyrimidine nucleoside.
Modification to the termini and conjugate groups
We modified siRNA by conjugation with aromatic compounds (such as hydroxyphenyl, phenyl, naphthyl, and pyrenyl derivatives), urea/thiourea bridged aromatic compounds, or polyethylene glycol (PEG).
Development of siRNA-Based Therapies
We help our customers develop siRNA-based therapeutics with the following features:
- Target essentially any gene in the genome
- Highly potent and long-lasting effects
- Modular and consistent performance across organs and diseases
- Administered in multiple ways, such as intravenous and inhalation delivery.
With our advanced siRNA synthesis and modification technologies and siRNA delivery platforms, our company is well-positioned to help our customers develop siRNA-based therapies for rare diseases. We believe our best-in-class technology and expertise in genetics have the potential to accelerate the development of precision drugs for rare diseases. If you are interested in our services, please contact us for more details.
Reference
- Kim, Y. K. RNA therapy: rich history, various applications and unlimited future prospects. Experimental & Molecular Medicine, 2022, 54(4): 455-465.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.