Antisense oligonucleotides (ASOs) are a single-stranded DNA or RNA sequence consisting of 15-25 nucleotides paired with a target gene. It can regulate gene expression by blocking the transcription or translation of target genes. Antisense oligonucleotides have been widely used in gene therapy due to their advantages of high specificity, high efficiency, and low toxicity.
In recent years, ASOs have often been used to develop gene-targeted therapy drugs. Natural ASOs are easily degraded in vivo with low specificity and toxic side effects. However, the ASO drugs usually have specific modifying groups to enhance the stability of oligonucleotides in vivo, improve their specificity, and reduce their toxic side effects.
Synbio Technologies has established production workshops that meet the quality management requirements of ISO 9001 and ISO 13485, with a standard production process and excellent synthesis & purification technologies. Our synthetic ASOs strictly comply with QC testing standards. HPLC purity detection is used to ensure the high quality output of all our ASO products.
- Manufacturing Capability: Microgram-to-gram-scale quantity can meet customers’ requirements from R&D level to manufacturing level.
- Delivery Speed: Flexible project arrangement, while providing the fastest delivery turnaround time.
- Strict Quality Control: With ISO 9001 & ISO 13485 quality certifications, the quality of our products is strictly controlled.
- Quality Analysis: HPLC and LC-Mass analysis (endotoxin and bioburden detection can be provided for cell experiments).
- Specialized Support: Our team of nucleic acid synthesis experts, with more than 18 years of experience, provides professional technical support.
- Highly Customized: We can provide various modification types and flexible synthesis specifications.
|ASO Synthesis||R & D level: ug-mg||HPLC||PTO, 2′-F, 2′-OME, 2′-MOE, LNA, Cholesterol, GalNAc, etc.||
|Manufacturing level: g||HPLC||PTO, 2′-F, 2′-OME, 2′-MOE, LNA, Cholesterol, GalNAc, etc.||
* If you need other special modifications or pricing, please contact us for a quote at email@example.com.
An increasing number of studies are identifying RNAi phenotypes by silencing antisense DNA oligonucleotides. ASO sequences are usually designed to bind to the mRNA of interest. ASOs are specifically hybridized to the target mRNA, which is specifically recognized by RNase H endonuclease, and the gene expression is blocked or inhibited by interfering with protein translation. The ASOs containing at least 6 bases of phosphorothioate-modified DNA fragments are combined with the target mRNA to form an RNA / DNA heteroduplex, which is the substrate of endogenous RNase H enzyme digestion [1-2]. qPCR is used to detect the decrease of mRNA level.
In addition to specific hybridization with target mRNA, ASOs can also be designed for the 5′- untranslated region of mRNA to block its translation. In addition, for precursor mRNA, ASOs can be designed at the splicing site of intron and exon to prevent a normal splice, which is called splicing arrest. This method has been successfully applied in the gene therapy of Duchenne Muscular Dystrophy (DMD) .
Ligand and ASO coupling is the main strategy for drug delivery of ASOs. Trivalent N-acetylgalactosamine (GalNAc, GN3) is a high-affinity ligand of the liver cell surface-specific asialoglycoprotein receptor (ASGPR), which can increase the efficacy of second-generation Gapmer ASOs in mouse liver cells by 6-10 times. Compared with MOE-modified ASOs, the combination of GalNAc conjugation and S-cEt modification can increase the ASOs efficiency by 60 times. GalNAc-conjugated ASOs has a high affinity with ASGPR in mice, which can improve the targeting delivery ability of ASOs to mouse hepatocytes .
Reference Walder RY and Walder JA.Role of RNase H in hybrid-arrested translation by antisense oligonucleotides. Proc Natl Acad Sci USA, 1988, 85:5011‒5015. Dagle JM, Walder JA, and Weeks DL. Targeted degradation of mRNA in Xenopus oocytes and embryos directed by modified oligonucleotides: studies of An2 and cyclin in embryogenesis. Nucleic Acids Res, 1990, 18:4751‒4757.Wang XL, Xian JN, Chen G, et al. Therapeutic oligonucleotides: a review. Chin J Biotech, 2018, 34(5): 664–675.Prakash TP, Graham MJ, Yu JH, etc. Targeted delivery of antisense oligonucleotides tohepatocytes using triantennary N-acetylgalactosamine improves potency 10-fold in mice. Nucleic Acids Res. 2014, 42(13): 8796-807.