The burgeoning domain of therapeutic oligonucleotides—encompassing antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs)—heralds a transformative epoch in precision medicine, facilitating direct engagement with hitherto intractable genes and their regulatory machinery. These succinct, synthetically engineered DNA or RNA strands exercise precise modulation of genetic expression. The pivotal determinant for realizing their complete therapeutic potential resides in deliberate chemical alteration. Our specialized oligonucleotide modification service at CD BioGlyco is meticulously calibrated to surmount extant pharmacokinetic and pharmacodynamic constraints. Through the strategic incorporation of proprietary and established modifications targeting the nucleobase, sugar moiety, or phosphate backbone, we convert preliminary oligo sequences into potent, durable, and cell-permeant drug candidates. This offering is indispensable for expediting the hit-to-lead progression and lead refinement phases within nucleic acid pharmaceutical development, guaranteeing that candidates exhibit superior stability, enhanced binding affinity, and targeted tissue delivery.
Our service is built upon a versatile, state-of-the-art platform encompassing the full spectrum of chemical and structural modifications necessary for next-generation oligonucleotide therapeutics.
The stability and target binding affinity of an oligonucleotide are fundamentally controlled by its backbone and sugar chemistry. We offer all clinically validated modifications:
The most common backbone modification, where a non-bridging oxygen is replaced by sulfur. PS linkages significantly confer nuclease resistance, which is vital for extending the in vivo half-life and promoting cellular uptake.
These sugar modifications increase nuclease resistance and enhance the binding affinity to the target RNA. 2'-MOE is particularly utilized in the "wings" of ASO gapmers to increase affinity and shield the RNase H-competent region.
LNA and other BNA analogs constrain the ribose ring, leading to unprecedented increases in target binding affinity and stability, enabling the design of shorter, more potent oligonucleotides.
Journal: Pharmaceutics
IF: 5.5
DOI: 10.3390/pharmaceutics14020260
Published: 2022
Results: This comprehensive review provides an overview of the development, mechanisms, and patent landscape of therapeutic oligonucleotides. The authors detail how these synthetic nucleic acids, including ASOs and siRNAs, modulate gene expression to treat diseases by targeting RNA or DNA. The article highlights key advancements in chemical modifications, such as phosphorothioate backbones and 2'-O-methoxyethyl groups, which enhance stability and efficacy, and delivery strategies like GalNAc conjugation for liver-specific targeting. It chronicles the clinical success of approved drugs, such as nusinersen for spinal muscular atrophy and inclisiran for hypercholesterolemia, and discusses the ongoing expansion into new therapeutic areas. Furthermore, the review analyzes the complex intellectual property strategies for protecting these novel therapeutics, examining the differing approaches of patent offices like the EPO and USPTO. The authors conclude that oligonucleotides represent a rapidly growing and promising class of drugs with the potential to target previously undruggable pathways.
Our service can be used to significantly enhance the stability of oligonucleotides against degradation by nucleases in blood and tissues, thereby prolonging their half-life and therapeutic effect.
Our service can be used to improve the absorption, distribution, and cellular uptake of oligonucleotides, leading to more favorable pharmacokinetic properties and increased bioavailability at the target site.
Our service can be used to strengthen the hydrogen bonding and hydrophobic interactions between the oligonucleotide and its target mRNA, resulting in heightened binding affinity and reduced off-target effects.
Our service can be used to mitigate unintended activation of the innate immune system by strategically modifying certain sequence motifs recognized by immune receptors.
Our service can be used to conjugate ligands or design chemistries that promote receptor-mediated uptake in specific cell types, enabling targeted delivery and improving intracellular trafficking.
Our service can be used to rapidly generate and screen a diverse library of modified candidates, streamlining the early-stage drug discovery pipeline for nucleic acid therapeutics.
— Dr. Hayes, Senior Investigator, Translational Medicine
— Manager, Drug Manufacturing
— Lead Scientist, In Vivo Pharmacology
While our therapeutic oligonucleotide modification service enables precise functionalization of nucleic acid therapeutics, the foundation of these advanced applications relies on high-quality starting materials. Our Chemical-based Oligonucleotide Synthesis Service provides this essential groundwork through both Solid-phase and Liquid-phase chemical synthesis platforms, offering comprehensive solutions for oligonucleotide production.
CD BioGlyco positions itself as a specialized collaborator for advancing precision medicine, offering a service focused on modifying therapeutic oligonucleotides. By integrating deep scientific experience with ongoing innovation in chemical synthesis, the company facilitates a continuous and efficient operational pathway, guiding each project from initial concept through to the completion of a rigorously refined end product. Contact us to enhance molecular stability, improve targeting accuracy, and increase pharmacological potency—attributes essential for transforming genetic discoveries into promising drug candidates.
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