Oligonucleotide Discovery & Design

The discovery and design of an oligonucleotide therapeutic require careful consideration of target biology, sequence characteristics, chemical modification, molecular stability, delivery requirements, and downstream manufacturability. Protheragen provides integrated oligonucleotide discovery & design services to support the early development of ASO, siRNA, and other oligonucleotide drug candidates, helping clients move efficiently from target concepts and sequence design to optimized candidates and conjugation strategies.

Overview of Oligonucleotide Discovery & Design

Oligonucleotide discovery & design is an important early stage in the development of nucleic acid therapeutics, involving the identification, design, screening, and optimization of oligonucleotide candidates against specific molecular targets. Unlike conventional small-molecule drug discovery, oligonucleotide development is highly dependent on sequence-specific interactions, chemical modification, molecular structure, and delivery characteristics.

The design process typically considers factors such as target selection, sequence specificity, target accessibility, chemical modification, molecular stability, potential off-target effects, and biological activity. Depending on the therapeutic mechanism, different oligonucleotide modalities, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), PMOs, and other modified oligonucleotides, may require different design and optimization strategies.

Oligonucleotide discovery may also incorporate conjugation technologies to improve delivery or introduce tissue- or cell-targeting capabilities. Conjugation strategies can involve small molecules, peptides, antibodies, or other functional moieties, with the choice of conjugate and linker architecture depending on the intended therapeutic application.

Fig.1 Common chemical modifications used in oligonucleotide drugs. (Moumné, L, et al., 2022)

Our Services

Successful development of oligonucleotide therapeutics begins with rational molecular design and optimization strategies. Early decisions regarding sequence selection, chemical characteristics, and delivery approaches can significantly influence therapeutic activity, specificity, stability, and downstream manufacturing feasibility.

Protheragen provides integrated oligonucleotide discovery and design services to support the identification and optimization of promising candidates. Our capabilities combine sequence design, target evaluation, and conjugation technology development to help establish oligonucleotide candidates with improved development potential and suitable characteristics for further CMC advancement.

Oligonucleotide Modalities We Support

• ASO - Antisense Oligonucleotides

ASOs are single-stranded oligonucleotides designed to modulate gene expression through sequence-specific interactions with RNA. Protheragen supports ASO sequence design and candidate development with consideration of sequence characteristics, chemical modification, stability, and downstream development requirements.

• siRNA - Small Interfering RNA

siRNA therapeutics use RNA interference mechanisms to selectively reduce the expression of target genes. Candidate development may involve sequence selection, strand considerations, chemical modification, and delivery-related design.

• PMO - Phosphorodiamidate Morpholino Oligomers

PMOs are chemically modified antisense molecules with a distinctive backbone structure. Their development requires consideration of sequence design, molecular properties, synthesis requirements, and downstream formulation or delivery strategies.

• Targeted Oligonucleotide Conjugates

Conjugated oligonucleotides can incorporate targeting or functional moieties such as small molecules, peptides, or antibodies. Such approaches can support the development of targeted delivery strategies and expand the potential applications of oligonucleotide therapeutics.

Key Development Considerations

Applications of Oligonucleotide Discovery & Design

Our services can support the early development of:

• Antisense oligonucleotide (ASO) therapeutics
• Small interfering RNA (siRNA) therapeutics
• PMO therapeutics
• Chemically modified oligonucleotides
• Targeted oligonucleotide conjugates
• Oligonucleotide–small molecule conjugates
• Oligonucleotide–peptide conjugates
• Oligonucleotide–antibody conjugates
• Other emerging nucleic acid therapeutic modalities

Why Choose Protheragen

• Integrated Oligonucleotide Development

Our discovery services are designed to connect sequence design, chemical modification, conjugation, process development, analytical development, and manufacturing within a broader CDMO workflow.

• Experienced Oligonucleotide Scientists

An experienced scientific team supports oligonucleotide development programs covering sequence design, solid-phase synthesis, conjugation technology, and CMC process development.

• Conjugation Technology Platform

The platform supports the development of conjugated oligonucleotides involving small molecules, peptides, and antibodies, providing options for targeted delivery strategies.

• Development-Oriented Candidate Selection

Candidate design considers not only biological objectives but also molecular properties, synthesis requirements, stability, analytical characterization, and downstream manufacturability.

• Seamless Transition to CMC

Selected candidates can transition into subsequent Solid-phase Synthesis Route Development, CMC Process Development, Oligonucleotide API Development, Analytical Services, and Manufacturing.

• Scalable Development Strategy

Our integrated oligonucleotide CDMO model supports progression from early research and candidate development toward process development, scale-up, and drug substance manufacturing.

From sequence discovery and candidate design to conjugation technology and downstream CMC development, Protheragen provides an integrated approach to oligonucleotide drug development. Whether you are developing an ASO, siRNA, PMO, or targeted oligonucleotide conjugate, our team can support the transition from early candidate concepts toward a development-ready molecule and subsequent manufacturing program. Contact Us to discuss your oligonucleotide development project and identify the appropriate discovery, design, and CDMO strategy for your program.