BOC RNA provides antisense oligonucleotides (ASOs) synthesis services according to your application to meet the research needs in biology, diagnostics, and drug discovery.
Antisense oligonucleotides are short, synthetic nucleic acid molecules that can be designed to specifically target mRNA molecules and prevent them from being translated into proteins. These molecules have gained a great deal of attention in recent years due to their potential to treat various genetic diseases by targeting disease-causing mutations or controlling overexpression of certain proteins.
Antisense oligonucleotides work by binding to the target mRNA molecule through complementary base pairing, either by Watson-Crick or Hoogsteen base pairing. This binding can occur in several different ways, such as blocking the ribosome from accessing the mRNA, recruiting RNase H to induce degradation of the mRNA or inhibiting alternative splicing events. The effectiveness of the molecule depends on several factors, including the length and position of the antisense oligonucleotide relative to the target mRNA, the degree of complementarity, and the stability of the resulting duplex structure. The specificity of the antisense oligonucleotide is critical to avoid off-target effects that could cause unintended toxicity and harm.
Antisense oligonucleotides are not readily taken up by cells and require a delivery mechanism to reach their target mRNA. There are several ways to deliver antisense oligonucleotides to cells, including chemical modifications to the oligonucleotide backbone, conjugation to various delivery vehicles, and encapsulation in nanoparticles. Chemical modifications can improve the stability and affinity of the molecule and reduce immunogenicity. Conjugation to delivery vehicles, such as liposomes or proteins, can enhance cellular uptake and improve tissue distribution. Encapsulation in nanoparticles can further protect the oligonucleotide from degradation and offer a sustained-release mechanism.
Antisense oligonucleotides have shown promise in treating various genetic disorders, including inherited genetic diseases, cancer, and viral infections. One of the most well-known applications of antisense oligonucleotides is in treating spinal muscular atrophy (SMA), a debilitating neuropathy caused by mutations in the SMN1 gene. In this case, antisense oligonucleotides are designed to increase the production of the SMN2 gene, which compensates for the loss of SMN1. Other applications of antisense oligonucleotides include treating Duchenne muscular dystrophy, Huntington's disease, and familial hypercholesterolemia.
mRNA folding into the secondary or tertiary structure is likely to prevent ASOs hybridization. Therefore, the unfolded mRNA region should be selected as the hybridization site.
Once the unfolded region is determined, it should be considered whether the region serves as a binding site for spliceosome, ribosome, protein, or other macromolecular assemblies, such as 5'cap, initiation codon, 3'untranslated region/polyA tail. Even if ASOs fail to activate RNase H, it can spatially block the mechanisms required for mRNA maturation or translation, which may lead to silencing.
In vivo and in vitro, nuclease activity quickly renders all-natural DNA ASOs useless. All ASOs need to be chemically modified to resist nuclease degradation to be effective.
1. Technical consulting: We provide technical consulting in genetics and molecular biology, including services for site selection, design, purification and characterization of Antisense Oligonucleotides.
2. ASO design: Select appropriate ASO for specific cells or tissues according to customer needs.
3. Synthetic ASO: We provide fully automated synthesis techniques and manual synthesis techniques to meet the different requirements of our customers.
| Types of ASOs Modifications | Abbreviation | Features |
| 5-methylcytosine | 5-Me-dC ([5MedC] in sequence constructs) | Replacing dC with 5-methyl dC in the CpG motif will slightly increase the Tm of the antisense oligo. |
| 7-deaza-dG | Deaza-Dg | |
| Methyl RNA | 2'-OMe-RNA ([mA], [mC], [mG], & [mU] in sequence constructs) | Add modified bases in chimeric antisense designs, such as 2'-O-methoxyethyl (2'-MOE) to increase nuclease stability and affinity (Tm). |
| Phosphorothioate | PS (* in sequence constructs) |
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| LNA | Locked nucleic acid |
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4. Sample collection: Sample collection and shipping services are provided to ensure that the ASO received from cells and tissues is of high quality and purity.
5. Quality control: Quality control of ASO by various analytical means, including high performance liquid chromatography (HPLC), mass spectrometry, polyacrylamide gel electrophoresis (PAGE), etc.
6. Data analysis: Provide data analysis services to assess the potency and specificity of ASO, as well as potential side effects and toxicity.
7. Service report: Provide detailed service report including information on ASO synthesis conditions, purification, quality control and data analysis.
Contact us now to get technical advice and more information. Our technical support team will review your inquiries or provide a quotation as soon as possible!
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