Inquiry

Oligonucleotide Modification Service

The Exciting Potential of Oligonucleotide Modification

Oligonucleotide modification involves precise adjustments to nucleic acid structure, including sugar backbone, bases, linkers, and fluorophores. These changes augment stability, binding, and specificity, broadening applications across disciplines. Modified oligonucleotides are crucial in gene therapy, modulating expression, rectifying mutations, and targeting pathogenic sequences. Diagnostic use leverages them for precise genetic variants and pathogen identification. Additionally, these modified strands play pivotal roles in RNA interference, gene silencing, and aptamer-mediated drug delivery. Bridging fundamental research with practicality, oligonucleotide modification propels progress in personalized medicine, molecular biology, and biotechnology, fostering innovation across fields.

Fig.1 Common chemical modifications in antisense oligonucleotides. (Khan, et al., 2021)

Key Technologies

Our service is founded on state-of-the-art solid-phase synthesis and advanced chemical conjugation techniques. We utilize a highly controlled, automated phosphoramidite chemistry workflow for the initial synthesis of the oligonucleotide chain. At specific points in the synthesis, or after the full sequence is complete, we introduce a variety of chemical modifications using specialized reagents and conjugation methods. These core technologies allow for the precise and reproducible incorporation of modifications at various positions, including the phosphate backbone, the sugar ring, the nucleobase, and at the 5' or 3' termini.

Modify to Magnify: Precision-Engineered Oligos.

Based on oligonucleotide structure, CD BioGlyco has developed several oligonucleotide-based modification services for clients to study the optional application of oligonucleotide analogs. Besides oligonucleotide-based modification services, CD BioGlyco also offers Custom Oligonucleotide Synthesis Services and Nucleoside & Nucleotide Modification Services for the generation of a better custom research proposal for our clients.

Oligonucleotide-based Phosphorylation Modification Service

Modification of oligonucleotide phosphate groups to alter their properties and functions.

Oligonucleotide-based Phosphorothioate Backbone Modification Service

Oligonucleotide phosphorothioate modification replaces non-bridging oxygen with sulfur, enhancing stability and binding affinity.

Oligonucleotide-based Sugar Ring Modification Service

Oligonucleotide sugar ring modifications alter deoxyribose/ribose, improving stability, selectivity, and pharmacokinetics.

Oligonucleotide-based Bases Modification Service

Oligonucleotide base modifications alter nucleotide structure, enhancing binding specificity, stability, and function for applications including gene silencing and diagnostics.

Oligonucleotide-based Linker Modification Service

Oligonucleotide linker modification changes connecting segments, influencing spatial arrangement and interactions.

Oligonucleotide Fluorophore Modification Service

Oligonucleotide fluorophore modification incorporates fluorescent molecules, enabling visualization and tracking of DNA/RNA, pivotal in imaging and molecular studies.

Workflow

Our oligonucleotide modification service follows a refined workflow designed for precision and reliability, ensuring that every custom-modified oligonucleotide is delivered with the highest quality.

Automated Solid-Phase Synthesis

The oligonucleotide is synthesized on a solid support using an automated synthesizer. This process involves the stepwise addition of phosphoramidite monomers, building the oligonucleotide chain from 3' to 5'.

Modification Incorporation

At the designated positions, custom modifications are introduced. This can involve using modified phosphoramidites during synthesis for base or sugar modifications or performing post-synthesis conjugation for labels and linkers at the termini.

Cleavage, Deprotection, and Purification

Once synthesis and modification are complete, the oligonucleotide is cleaved from the solid support and undergoes a deprotection step to remove protecting groups. The crude product is then purified using methods such as HPLC or PAGE to isolate the full-length, modified oligonucleotide from truncated sequences and other impurities.

Quality Control and Final Delivery

Every modified oligonucleotide undergoes rigorous quality control to verify its purity and identity. We use advanced analytical techniques, including mass spectrometry, to confirm the molecular weight and purity.

Our workflow. (CD BioGlyco)

Publication Data

DOI.: 10.1093/nargab/lqae058

Journal: NAR Genomics and Bioinformatics

Published: 2024

IF: 2.8

Results: This study developed and validated new molecular dynamics force field parameters for phosphorothioate (PS)-modified therapeutic nucleic acids to enable accurate atomistic simulations. The authors derived parameters through quantum mechanical calculations on dimethyl phosphorothioate (DMPT), optimizing bond lengths, angles, and dihedral terms involving the sulfur atom. They validated these parameters in 2 μs MD simulations across three systems: PS-modified B-DNA, an RNA hairpin with a single-nucleotide bulge, and a DNA:RNA hybrid duplex. Comparative analyses with natural (phosphate-linked) counterparts revealed that PS modifications induced bimodal twist distributions in CpG steps of B-DNA and increased conformational flexibility in the bulged nucleotide of RNA, while showing minimal impact on the DNA:RNA hybrid structure. These findings highlight PS-backbone effects on nucleic acid dynamics relevant to antisense oligonucleotide design.

Applications of Oligonucleotide Modification Service

Modified oligonucleotides serve as probes for detecting genetic variations, pathogens, and disease markers in techniques like PCR, qPCR, and DNA microarrays.
Modified siRNAs and miRNAs silence genes at the post-transcriptional level, advancing therapeutics for cancer, viral infections, and neurodegenerative diseases.
Fluorophore-labeled oligonucleotides aid in visualizing and tracking nucleic acids, proteins, and cellular processes using techniques like FISH and live-cell imaging.
Modified RNA sequences in mRNA vaccines enable targeted protein production, revolutionizing rapid vaccine development and distribution.
Modified oligonucleotides are pivotal for techniques like RNA-seq and ChIP-seq, enabling detailed analysis of gene expression and epigenetic modifications.

Highlights of Our Oligonucleotide Modification Service

CD BioGlyco built a well-equipment lab for our synthesis platform, which provides high-quality outcomes for our clients.
CD BioGlyco lab team exhibits strong attention to detail and follows rigorous quality control measures, ensuring the accuracy and precision of their experimental procedures and analysis.

Frequently Asked Questions

Associated Services

Our oligonucleotide modification enables precise tailoring of nucleic acid properties (e.g., nuclease resistance, binding affinity) for therapeutic and diagnostic research. To ensure a robust supply of high-purity molecular building blocks for these advanced modifications, we offer targeted Nucleoside Production Services:

(AI-CD BioGlyco)

CD BioGlyco provides custom oligonucleotide modification services for our clients, if you have any questions or require details information, please feel free to contact us.

References

Khan, P.; et al. RNA-based therapies: A cog in the wheel of lung cancer defense. Molecular cancer. 2021, 20: 1-24. (Open Access)
Carlesso, A.; et al.. Structural dynamics of therapeutic nucleic acids with phosphorothioate backbone modifications. NAR Genomics and Bioinformatics. 2024, 6(2): lqae058. (Open Access)

This service is for Research Use Only, not intended for any clinical use.