Services

Online Inquiry

Your Name

Phone Number

* E-mail Address

* Services Interested

Project Description

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 End Modification

At Protheragen BioNucleics, we specialize in advancing oligonucleotide therapeutics through innovative modification services. With a focus on siRNA end modification, our expertise enables us to enhance the stability, efficacy, and specificity of siRNA molecules for various applications. Discover more about our Oligonucleotide Drugs CRO, Oligonucleotide Modification Service, and siRNA Modification Service.

Overview of siRNA End Modification

Small interfering RNA (siRNA) end modification is a crucial process in optimizing siRNA-based therapeutics. By altering the 5' and 3' ends of siRNA molecules, we can significantly enhance their resistance to nuclease degradation, improve pharmacokinetic properties, and increase gene-silencing efficiency. End modifications facilitate better interaction with the RNA-induced silencing complex (RISC), ensuring precise gene targeting and minimal off-target effects. This advancement is pivotal in the development of effective and reliable RNA interference (RNAi) therapies.

Fig.1 An illustration of the proposed mechanism shows how substituting siRNA with SNA leads to a reduction in off-target activity. Fig.1 Schematic illustration of the proposed mechanism, by which serinol nucleic acid (SNA)-substituted siRNA reduces off-target activity (Kamiya, et al., 2020).

Our Services

At Protheragen BioNucleics, we offer comprehensive siRNA end modification services utilizing cutting-edge technologies to meet your research and therapeutic needs. Our key services include:

siRNA 5' End Modification

Phosphorylation: Adding a phosphate group to the 5' end to enhance recognition by enzymes and improve RNA-induced silencing complex (RISC) loading efficiency.
Fluorescent Labeling: Attaching fluorescent dyes to the 5' end for visualization and tracking of siRNA within biological systems.
Biotinylation: Incorporating biotin moieties at the 5' end for purification, immobilization, or detection purposes. Biotinylated siRNA can be captured using streptavidin-coated surfaces, facilitating various biochemical applications.
Chemical Capping: Using protective groups to cap the 5' end, preventing degradation by exonucleases and enhancing stability.
Thiol Modification: Introducing thiol groups (-SH) at the 5' end to enable covalent attachment to maleimide-containing molecules. This modification is essential for conjugating siRNA to carriers like nanoparticles, peptides, or proteins for targeted delivery.
Amino (NH₂) Modification: Adding amino groups at the 5' end allows for further conjugation with functional molecules such as dyes, drugs, or polymers through amide bond formation, expanding the versatility of siRNA applications.

siRNA 3' End Modification

Cholesterol Conjugation: Enhancing cellular uptake and membrane permeability by attaching cholesterol molecules to the 3' end. This modification promotes association with lipoproteins, facilitating efficient delivery to target cells without the need for transfection agents.
Inverted dT Modification: Adding inverted deoxythymidine residues at the 3' end to protect against exonuclease activity, thereby increasing the stability of siRNA molecules in biological environments.
Poly(A) Tail Addition: Improving nuclease resistance and prolonging half-life in biological fluids by adding a polyadenine tail at the 3' end.
Fluorescent and Quencher Labels: Attaching fluorescent dyes or quenchers at the 3' end to facilitate real-time PCR, fluorescence resonance energy transfer (FRET) applications, and tracking of siRNA molecules.
Thiol Modification: Introducing thiol groups (-SH) at the 3' end for covalent coupling with maleimide-functionalized entities, enabling the creation of siRNA conjugates for specialized delivery systems.
Amino (NH₂) Modification: Adding amino groups at the 3' end for conjugation with various functional molecules, enhancing the capability to customize siRNA for specific research needs.

Customized siRNA Linker and Spacer Incorporation

PEGylation: Attaching polyethylene glycol (PEG) chains to increase solubility, reduce immunogenicity, and enhance the pharmacokinetic profile of siRNA molecules.
Cleavable Linkers: Introducing linkers that respond to specific stimuli (e.g., pH changes, enzymatic activity) for controlled release of siRNA at the target site.
Spacer Molecules: Optimizing the distance between functional groups and the siRNA molecule by incorporating spacer units, improving interaction with target molecules and reducing steric hindrance.

siRNA Conjugation to Targeting Ligands

Antibody-siRNA Conjugates: Combining siRNA with antibodies to achieve targeted delivery to specific cell types or tissues, enhancing therapeutic efficacy and reducing off-target effects.
Aptamer Attachment: Using nucleic acid aptamers to direct siRNA to particular cellular receptors, providing high specificity and affinity in targeting.
Peptide Conjugation: Enhancing intracellular delivery through the attachment of cell-penetrating peptides (CPPs) to siRNA, facilitating efficient translocation across cellular membranes.

Why Choose Us

Expertise and Experience: Our team consists of leading scientists with extensive knowledge in siRNA technology and oligonucleotide chemistry.
Tailored Solutions: We provide customized services specifically designed to meet your project's unique requirements.
Comprehensive Support: From initial consultation to final delivery, we offer full-spectrum support, including technical assistance and after-sales service.

Reference

Kamiya, Y.; et al. Investigation of strand-selective interaction of SNA-modified siRNA with AGO2-MID. International Journal of Molecular Sciences. 2020, 21(15): 5218.

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.