AntimiR oligonucleotides, known as anti-miRs or antagomirs, are a critical class of synthetic nucleic acids in the burgeoning field of therapeutic oligonucleotide development. These molecules are specifically engineered to inhibit the function of endogenous microRNAs (miRNAs). MicroRNAs are small, non-coding RNAs that play pivotal roles in regulating gene expression. Dysregulated miRNA activity is increasingly implicated in a vast array of diseases, from cancer and viral infections to cardiovascular disorders. At CD BioGlyco, the antimiR synthesis service provides researchers and pharmaceutical developers with high-purity, chemically modified, single-stranded oligonucleotides complementary to target miRNAs. By binding to and sequestering the mature miRNA, our expertly synthesized anti-miRs prevent the miRNA from binding to its target messenger RNA (mRNA), thereby restoring or modulating gene expression. Our commitment to precision and performance ensures your therapeutic and research targets are met with superior-quality materials.
Solid-phase Synthesis (SPS)
The backbone of our service is highly-optimized SPS a refined methodology that allows for the sequential addition of nucleotide building blocks. This automated, high-throughput approach is essential for synthesizing oligonucleotides of defined sequence, length, and purity, ensuring batch-to-batch consistency.
Strategic Chemical Modifications
To enhance nuclease resistance, cellular uptake, and binding affinity, we strategically incorporate a variety of chemical modifications. Key modifications include 2'-O-Methyl (2'-OMe) and 2'-O-Methoxyethyl (2'-MOE) substitutions on the ribose sugar, which significantly increase the binding affinity to the target RNA and confer resistance to nuclease degradation.
As a key component of our therapeutic oligonucleotide synthesis service within the broader therapeutic nucleic acid development platform, our AntimiR synthesis service is centered on providing highly customized inhibitory molecules. Our service provides the synthesis of anti-miRs with a comprehensive range of chemical enhancements, including:
Our experts collaborate with you to define the precise target miRNA, desired modifications (e.g., 2'-OMe, LNA, conjugation), and synthesis scale. We offer tailored design optimization services to recommend the most potent and specific antimiR sequence and modification strategy for your specific biological application.
The optimized antimiR sequence is manufactured using advanced automated DNA/RNA synthesizers. We utilize high-quality, ultra-pure phosphoramidite building blocks in the SPS process, which operates under strictly controlled, anhydrous conditions to ensure high coupling efficiency and minimal truncations.
Following successful chain assembly, the fully protected oligonucleotide is chemically cleaved from the solid support and simultaneously deprotected of base and phosphate protection groups. This step is meticulously optimized to maximize the yield of the full-length product while minimizing side reactions.
Crude oligonucleotides undergo rigorous purification to remove truncated sequences, failed synthesis products, and protecting group remnants. We utilize high-performance liquid chromatography (HPLC), and for certain high-purity requirements, polyacrylamide gel electrophoresis (PAGE), to achieve purity levels up to >98%, essential for in vivo studies.
A comprehensive quality control (QC) process is mandatory for all synthesized anti-miRs. Every batch is validated using mass spectrometry (MS) to confirm the correct molecular weight, verifying the sequence fidelity and the accurate incorporation of all chemical modifications. Analytical HPLC is used to confirm final purity.
For specialized research needs, we offer an array of post-synthesis modifications, including the conjugation of targeting ligands (e.g., cholesterol, GalNAc), reporter molecules (e.g., fluorescent dyes), or other functional groups to enhance delivery or enable detection.
DoI: 10.1038/ncomms15162
Journal: Nature Communications
IF: 15.7
Published: 2017
Results: This study develops a light-inducible antimiR-92a as a targeted therapy for impaired wound healing in diabetic mice. The antimiR-92a is modified with photolabile "cages" that block its activity until activated by 385 nm light. Intradermal injection and local irradiation specifically inhibit miR-92a in skin tissue without affecting other organs, avoiding systemic side effects. Activation derepresses miR-92a targets Itga5 and Sirt1, enhancing angiogenesis and wound cell proliferation. In healing-impaired db/db mice, light-activated antimiR-92a accelerates re-epithelialization, increases granulation tissue density, and strengthens wound contraction, matching the efficacy of conventional antimiRs. Toxicity tests confirm no liver or kidney damage. This proof-of-concept demonstrates light-controlled local antimiR activation as a safe, precise strategy for treating chronic wounds and potential other miR-related diseases.
Fig.1 Efficient miR-92a downregulation in the skin upon treatment with caged antimiR-92a. (Lucas, et al., 2017)
Cancer Research and Oncology
AntimiRs are used to silence oncogenic miRNAs that are overexpressed in tumors, helping to restore tumor suppressor functions, inhibit proliferation, and study metastasis mechanisms.
Cardiovascular and Metabolic Diseases
Research into conditions like fibrosis, atherosclerosis, and diabetes frequently targets disease-associated miRNAs. AntimiRs against miRNAs like miR-21 or those regulating lipid metabolism are key to understanding and potentially treating these disorders.
Infectious Disease Research
AntimiRs can be employed to target miRNAs involved in viral replication or host-pathogen interaction, offering a new avenue for developing antiviral therapies.
Validation and Functional Genomics
Academics and industry researchers utilize antimiRs as highly specific reagents to silence a single miRNA in vitro and in vivo, enabling the rapid and clear validation of gene targets and pathway elucidation.
Exceptional Oligonucleotide Purity
Our multi-stage purification protocols, including high-resolution HPLC, consistently deliver antimiRs with purity levels up to >98%, minimizing the risk of off-target effects and maximizing the reliability of your in vivo data.
Unrivaled Chemical Modification Expertise
Our deep expertise allows for the seamless, strategic incorporation of complex modifications (LNA, MOE, 2'-OMe) and targeting ligands, ensuring high nuclease stability and enhanced in vivo performance.
Rigorous MS and HPLC Analysis
Every synthesized antimiR is accompanied by a comprehensive certificate of analysis (CoA), including MS and analytical HPLC data, providing complete sequence and purity confirmation.
Custom Conjugation for Enhanced Delivery
Our advanced conjugation service allows for the attachment of crucial delivery moieties, offering a significant advantage in improving the pharmacokinetics and targeted tissue delivery of your therapeutic candidate.
"The LNA-modified antimiR for our challenging CNS target was delivered with exceptional purity. The MS data provided gave us the confidence to proceed directly to our in vivo model. The synthesis team at CD BioGlyco offered proactive communication throughout the process, significantly accelerating our preclinical timeline."
– R.S., Lead Research Scientist
"We required a gram-scale synthesis of a cholesterol-conjugated antagomir for a toxicology study. CD BioGlyco successfully scaled up the synthesis while maintaining >95% purity and ensuring excellent batch consistency. Their adherence to rigorous QC was instrumental in our successful research."
- P.H., Director of Process Chemistry
"The technical consultation we received for selecting the optimal 2'-MOE modification pattern for our target miRNA was outstanding. The final antimiR product demonstrated superior stability and potency in our cellular assays compared to previous vendors."
- L.W., Principal Investigator
CD BioGlyco is your trusted expert in the synthesis of high-quality, chemically tailored antimiR oligonucleotides. Leveraging our mastery of SPS, sophisticated chemical modifications, and rigorous multi-stage purification, we provide the reliable, high-purity tools necessary to drive your most ambitious research and therapeutic development goals. Please feel free to contact us to unlock the therapeutic potential of microRNA inhibition.
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