Oligonucleotide Conjugation Services

The development of oligonucleotide therapeutics begins with the identification of suitable target sequences and the design of molecules with the desired biological activity, specificity, stability, and development potential. Protheragen provides integrated Sequence Design & Discovery services to support the early development of ASO, siRNA, PMO, and other oligonucleotide therapeutics. By combining target evaluation, sequence design, candidate screening, chemical modification strategies, and development-oriented optimization, Protheragen helps identify promising oligonucleotide candidates and establish a clear path toward downstream synthesis, CMC development, and manufacturing.

Overview of Oligonucleotide Conjugation

Conjugation is an important strategy for improving the delivery, targeting, or functional properties of oligonucleotide therapeutics. By linking an oligonucleotide to an appropriate targeting or functional moiety, conjugation technologies can be used to influence tissue distribution, cellular uptake, molecular stability, and other development characteristics.

The selection of a suitable conjugation strategy requires consideration of the oligonucleotide modality, biological target, conjugation site, linker chemistry, molecular structure, and intended mechanism of action. Protheragen integrates these factors into a development-oriented conjugation workflow to support the design and optimization of oligonucleotide conjugates.

The platform can be applied to different oligonucleotide modalities and conjugation formats, supporting early-stage candidate exploration as well as subsequent analytical, process, formulation, and manufacturing development.

Fig.1 General methods to conjugate oligonucleotides. (Dugal-Tessier J, et al., 2021)

Our Services

Protheragen provides flexible conjugation technology support covering conjugation design, linker selection, conjugate preparation, characterization, and optimization. Services can be configured according to the molecular format and development objectives of each project.

Conjugation Formats Supported

• Oligonucleotide-Small Molecule Conjugates

Small-molecule conjugation can be used to introduce targeting or functional components to an oligonucleotide. Such approaches may support tissue-specific delivery or improve the functional characteristics of the therapeutic candidate.

• Oligonucleotide-Peptide Conjugates

Peptide conjugation can provide opportunities for receptor-mediated targeting, cellular uptake, or other delivery mechanisms. The peptide, linker, conjugation site, and oligonucleotide can be considered as an integrated molecular system.

• Oligonucleotide-Antibody Conjugates

Antibody-based conjugation can provide highly specific targeting capabilities. The design of antibody-oligonucleotide conjugates requires consideration of antibody properties, conjugation chemistry, linker selection, molecular stability, and downstream analytical requirements.

• Ligand-Oligonucleotide Conjugates

Ligands targeting specific receptors or transport pathways can be conjugated to oligonucleotides to support selective delivery to relevant cells or tissues. This approach can be considered for programs requiring receptor-mediated uptake.

• Other Functional Conjugates

Depending on project objectives, other functional or targeting components may be evaluated to create customized oligonucleotide conjugates with specific delivery or biological characteristics.

Key Conjugation Development Considerations

Conjugation Technology Development Workflow

The conjugation development workflow integrates molecular design, chemistry selection, conjugate preparation, characterization, and optimization to support the progression of promising candidates toward downstream development.

Why Choose Protheragen

• Integrated Molecular Design

Conjugation strategies can be evaluated together with sequence design, chemical modification, and oligonucleotide molecular characteristics to support a more integrated candidate development process.

• Flexible Conjugation Strategies

Protheragen supports multiple conjugation formats involving small molecules, peptides, antibodies, ligands, and other functional components, allowing conjugation approaches to be tailored to individual development programs.

• Development-Oriented Optimization

Candidate conjugates are evaluated not only for successful conjugation but also for molecular integrity, stability, analytical characteristics, and downstream development potential.

• Analytical Support

Conjugation development can be integrated with analytical characterization to evaluate conjugate identity, purity, molecular integrity, and other critical quality attributes.

• CMC Integration

Information generated during conjugation development can support subsequent synthesis route development, process development, analytical development, drug substance development, formulation, and manufacturing.

• Customized Project Design

Conjugation strategies can be adapted according to the oligonucleotide modality, therapeutic target, delivery objective, molecular format, development stage, and manufacturing requirements.

Protheragen provides integrated Oligonucleotide Conjugation Services services for the development of targeted and functionally optimized oligonucleotide therapeutics. By combining conjugation strategy design, linker and chemistry selection, conjugate preparation, analytical characterization, and candidate optimization, we support the development of oligonucleotide conjugates from early discovery through downstream CMC development and manufacturing. Contact us to discuss your oligonucleotide conjugation program and develop a customized strategy for your therapeutic candidate.