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Please note that we are not a pharmacy or clinic, so we are unable to see patients and do not offer diagnostic and treatment services for individuals.

siRNA Modification Service

At Protheragen BioNucleics, we specialize in advancing the therapeutic potential of oligonucleotide-based therapies through precision-driven solutions. Our expertise spans Oligonucleotide Drugs CRO and Oligonucleotide Modification Services, where innovation meets rigorous scientific validation. By leveraging decades of experience in nucleic acid chemistry, we empower researchers and biopharmaceutical partners to overcome challenges in the stability, delivery, and efficacy of siRNA therapeutics.

Overview of siRNA Modification Service

Small interfering RNA (siRNA) therapies hold transformative potential, but their clinical success hinges on strategic chemical modifications to enhance performance. Our siRNA modification service focuses on tailoring siRNA molecules to improve nuclease resistance, reduce off-target effects, and optimize cellular uptake. By systematically modifying specific regions of the siRNA structure—such as the sugar-phosphate backbone, nucleobases, or termini—we address pharmacokinetic and pharmacodynamic limitations. These enhancements are critical for achieving targeted gene silencing in vivo, particularly in complex biological environments.

Our Services

siRNA Sugar Modification

Modifying the ribose sugar moiety is pivotal for stabilizing siRNA against enzymatic degradation. We employ 2'-O-methyl (2'-OMe), 2'-fluoro (2'-F), and locked nucleic acid (LNA) substitutions to bolster RNAse resistance while maintaining silencing activity. These modifications also mitigate immune responses by reducing recognition by Toll-like receptors.

siRNA Phosphodiester Bond Modification

Replacing phosphodiester bonds with phosphorothioate (PS) linkages enhances siRNA stability in serum-rich environments. Our team optimizes PS placement to balance stability with minimal toxicity, ensuring prolonged half-life without compromising RNA-induced silencing complex (RISC) loading efficiency.

siRNA Nucleotide Base Modification

Chemical alterations to nucleobases, such as introducing 5-methylcytosine or dihydrouridine, prevent base-pairing errors and minimize off-target interactions. These modifications are tailored to preserve Watson-Crick pairing with the target mRNA while improving specificity.

siRNA Backbone Modification

We redesign the siRNA backbone using alternatives like peptide nucleic acids (PNAs) or morpholino oligomers to create nuclease-resistant structures. This approach is particularly valuable for systemic applications where prolonged circulation is required.

siRNA End Modification

Terminal modifications, including cholesterol conjugation or PEGylation, enhance siRNA delivery by promoting association with lipid carriers or prolonging circulatory half-life. We also incorporate targeting ligands (e.g., GalNAc) for tissue-specific uptake, significantly improving therapeutic indices.

siRNA Amino Acid Modification

Integration of amino acid-based linkers or peptide tags enables covalent conjugation with delivery vehicles or tracking probes. This innovation facilitates real-time biodistribution studies and targeted delivery to hard-to-reach tissues.

Frequently Asked Questions

Q1: Why are chemical modifications critical for siRNA therapeutics?

Modifications enhance stability, reduce immunogenicity, and improve delivery efficiency. Unmodified siRNAs are rapidly degraded in serum and often fail to reach target tissues at therapeutic concentrations.

Q2: How do sugar modifications differ from backbone alterations?

Sugar modifications (e.g., 2'-OMe) protect against exonuclease degradation, while backbone changes (e.g., PS linkages) resist endonucleases. Both strategies synergize to prolong siRNA activity.

Q3: Can modifications affect gene-silencing efficacy?

Properly optimized modifications maintain or enhance silencing by preserving RISC compatibility. Our iterative design process ensures the balance between stability and functionality.

Applications

Oncology

Silencing oncogenes or resistance genes in tumors.

Rare Diseases

Targeting mutant transcripts in genetic disorders.

Infectious Diseases

Inhibiting viral replication via host or pathogen gene silencing.

Neurology

Addressing neurodegenerative pathways with blood-brain barrier-penetrating siRNAs.

Why Choose Us

End-to-End Solutions: From design to in vivo validation.
Customized Delivery Strategies: Tailored conjugates for tissue-specific targeting.
Collaborative Innovation: Partner-focused workflows with rapid turnaround times.

Our services and products are exclusively for authorized organizations in research, development, or manufacturing and are not intended for direct use by individuals or patients or as medical advice, diagnosis, or treatment.