Phosphorothioate Modification Service

Introduction

Phosphorothioate (PS) modification replaces oligonucleotide backbone oxygen with sulfur, boosting nuclease resistance while retaining RNase H activity. It offers stability, better tissue penetration, and clinical relevance. We provide end-to-end services: custom design, hybrid modifications, and analytical excellence for robust, clinic-ready oligonucleotides.

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Phosphorothioates

Basics

Phosphorothioates PS replace a non-bridging oxygen atom in the phosphodiester backbone with sulfur creating a robust -O-P-S- bond that maintains the natural negative charge while conferring unique biological resilience this structural tweak allows the oligonucleotide to withstand enzymatic breakdown while retaining its ability to interact with target molecules

Key Advantages

Nuclease Resistance

Up to 5× longer serum half-life compared to unmodified oligonucleotides making them suitable for sustained therapeutic effects in vivo without frequent dosing.

Enhanced Cellular Uptake

Improved protein binding properties facilitate tissue specific delivery ensuring the oligonucleotide reaches its intended target cells more efficiently.

Balanced Immunogenicity

Optimal modification density reduces off target immune activation minimizing adverse reactions while preserving therapeutic efficacy.

Design Considerations

Site Specific Modification

Partial backbone modifications such as focusing on 3' or 5' ends help preserve target affinity while maximizing stability striking a balance between functionality and durability.

Diastereomer Control

Strict synthesis protocols ensure ≥98% purity eliminating stereoisomer driven toxicity which is critical for safe clinical application.

Workflow

1. Sequence Optimization

   Collaborate with our experts to design PS-modified sequences tailored to your target's GC content, secondary structures, and delivery route. Our team utilizes predictive algorithms to analyze potential off-target interactions and recommend modification patterns that strike a balance between stability and binding affinity, ensuring the sequence aligns with your specific therapeutic or diagnostic goals.

2. Precision Synthesis

   High-fidelity automated platforms synthesize PS-linked oligonucleotides under inert gas conditions to minimize sulfoxide byproducts that could compromise performance. Each coupling step is monitored in real time to ensure accurate sulfur incorporation, maintaining consistent backbone modification across the entire sequence.

3. Rigorous Quality Control

   Purity Validation

   HPLC and MS confirm ≤0.5% impurity levels, separating full-length products from truncated sequences or unmodified fragments to guarantee batch uniformity.

4. Functional Testing

   Includes nuclease resistance assays measuring degradation rates in serum, T_m profiling to verify target binding stability, and cell uptake studies using fluorescence labeling to track delivery efficiency.

5. Turnaround

   6-8 weeks for research-grade batches, with scalable production capabilities to GMP-compliant manufacturing, meeting the strict standards required for preclinical and clinical applications.

6. Deliverables

   Lyophilized PS-oligos with detailed stability data documenting performance under various storage conditions, comprehensive synthesis reports outlining modification efficiency, and custom formulation guidance to optimize solubility and handling for your specific experimental setup.

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What We Can Offer?

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Customer Reviews

"Our collaboration with Creative Biolabs on phosphorothioate-modified oligonucleotides has been instrumental in advancing our therapeutic program. Their proprietary design algorithms delivered sequences with exceptional target specificity, as off-target binding was reduced by over 40% compared to our previous iterations, directly lowering toxicity risks in preclinical models."

"The diastereomer-free synthesis process ensured remarkable batch consistency. Across three scale-up runs (from 10 mg to 500 mg), purity remained ≥99.2% by HPLC, and nuclease resistance profiles showed less than 2% variability. This reliability was critical as we transitioned from in vitro screening to in vivo efficacy studies."

"Their team's ability to align production with global regulatory standards, including ICH Q7-compliant documentation, streamlined our IND preparation. Perhaps most valuable was the 30% faster turnaround, which shaved 4 weeks off our development timeline. For complex PS-modified projects requiring precision and scalability, Creative Biolabs has proven to be an indispensable partner."

FAQs

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