Custom Oligonucleotide Modification Services

Introduction

Accelerate your nucleic acid research with our Custom Oligonucleotide Modification Service. We solve stability, specificity, delivery, and gene expression issues via advanced chemical modifications, enhancing research and drug development efficacy. Tailored solutions improve pharmacokinetics, address unmodified oligonucleotide flaws, and deliver stable, specific, potent products for gene therapy, diagnostics, etc.

Custom Oligonucleotide Modification Service is pivotal in molecular biology and drug development. Chemical modifications address unmodified nucleic acids' poor stability and uptake, enhancing nuclease resistance, binding affinity, and delivery. Creative Biolabs uses this expertise to provide superior modified oligonucleotides for diverse applications.

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Custom Oligonucleotide Modification Service

Oligonucleotide modification is the strategic chemical alteration of DNA/RNA at phosphate, sugar, or base, aiming to improve stability, binding affinity/specificity, cellular uptake, and add functionalities.

Fig.1 Various chemical modifications to the three important structural parts of deoxyribonucleic acid.¹

Common modification classifications and major category introductions of oligonucleotides

• Phosphate group modification: The chemical modification of phosphodiester bonds between nucleotides mainly enhances the enzymatic stability and bioavailability of oligonucleotides.
• Sugar ring modification: By modifying the structure of ribose or deoxyribose (such as the 2' position), the targeted binding ability and stability of oligonucleotides can be optimized.
• Base modification: Chemical modification of nucleotide bases can regulate base pairing characteristics, enhance targeting specificity, or introduce special functions.
• Terminal/functional group modification: Functional chemical groups are introduced at the end or specific positions of oligonucleotides for labeling, conjugation, or subsequent reactions.
• Marking and detection modification: Introduce detectable or identifiable molecules for tracking, imaging, or signal detection.

Tab.1 Custom oligonucleotide modifications available from Creative Biolabs.

Workflow

1. Required Starting Materials

   • Oligonucleotide Sequence: The precise DNA or RNA sequence requiring modification.
   • Desired Modification Type(s): Specific chemical modifications (e.g., phosphorothioate, LNA, fluorescent dyes, quenchers, attachment chemistries) and their intended positions.
   • Application Details: A brief description of the intended use (e.g., gene silencing, diagnostic probe) to help us optimize the modification strategy.

2. Project Consultation & Design: Our experts collaborate to understand requirements, design optimal modification strategies (selecting modifications, considering stability/specificity/delivery), outline synthesis plans, and deliver a detailed proposal with clear oligonucleotide design.

3. Custom Oligonucleotide Synthesis: State-of-the-art automated platforms precisely incorporate specified modifications at target positions, yielding raw synthesized modified oligonucleotides.

4. Deprotection & Cleavage: Post-synthesis, oligonucleotides are deprotected and cleaved from the solid support (removing protecting groups), resulting in a crude mixture.

5. Purification: Advanced techniques (desalting, PAGE, HPLC), chosen by length and required purity, remove truncations/impurities, producing highly pure, full-length modified oligonucleotides.

6. Quality Control & Analysis: Rigorous QC via MS and analytical HPLC confirms sequence integrity, modification incorporation, and purity, with a comprehensive report verifying characteristics.

7. Final Deliverables

   • Purified Modified Oligonucleotide: Lyophilized in a tube or plate format, ready for your experiments.
   • Detailed Quality Control Report: Including mass spectrometry data, analytical HPLC chromatograms, and purity assessments.
   • Synthesis Report: Documenting the specific modifications incorporated and the synthesis parameters.

8. Estimated Timeframe: The service typically takes 3-6 weeks, depending on modification complexity, oligonucleotide length, and required purity. More complex/novel modifications may extend the timeline slightly.

What we can offer

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Customer Reviews

"Using Creative Biolabs' Custom Oligonucleotide Modification Service in our research has significantly improved the in vivo stability of our antisense oligonucleotides, which was a major bottleneck in our preclinical studies."

October 2024, Dr. A***n

"The site-specific modifications provided by Creative Biolabs for our sgRNA constructs have greatly facilitated our gene editing experiments, leading to much higher editing efficiencies and reduced off-target activity."

September 2024, Dr. L***a

"We rely on Creative Biolabs for our diagnostic probe modifications. Their consistent quality and the precise incorporation of fluorescent dyes have been critical for the success of our high-throughput screening assays."

November 2024, Dr. M***s

FAQ

Creative Biolabs' Custom Oligonucleotide Modification Service is your premier partner for nucleic acid research and therapeutic development. Offering extensive chemical modifications, strict quality control, and expert consultation, we help overcome unmodified oligonucleotide limitations, unlock their potential, and accelerate discoveries with tailored solutions.

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Reference

1. Baker, Ysobel R., et al. "An LNA-amide modification that enhances the cell uptake and activity of phosphorothioate exon-skipping oligonucleotides." Nature Communications 13.1 (2022): 4036. DOI: 10.1038/s41467-022-31636-2. Distributed under Open Access license CC BY 4.0, without modification.