January 2026
The Future of Oligonucleotide Therapeutics: Innovations in Chemistry, Discovery, and Delivery
Oligonucleotide therapeutics are entering a pivotal phase. Once limited to rare genetic diseases, antisense oligonucleotides, RNA interference (RNAi), and other nucleic acid–based therapeutics are now expanding into neurology, cardiometabolic disease, oncology, and immunology.
This shift is being driven by breakthroughs in oligonucleotide chemistry, synthesis, manufacturing, and targeted delivery — all of which are redefining how RNA medicines are discovered, developed, and scaled. At TIDES USA 2026, leading scientists and drug developers will share how these innovations are turning RNA modalities into mainstream therapeutics.
1. Oligonucleotide Chemistry Is Enabling Drug-Like RNA Medicines
Early oligonucleotide programs struggled with instability, immunogenicity, and off-target effects. Today, advances in backbone chemistry, sugar modifications, and conjugation strategies are transforming oligonucleotides into precision-designed therapeutics.
Next-generation chemistries are enabling:
Increased stability and circulation time
Cell- and tissue-specific activation
Lower therapeutic doses with improved safety
Greater durability with less frequent dosing
These innovations are redefining what “drug-like” means for RNA-based medicines.
At the conference, this evolution is reflected in sessions exploring conditionally activated oligonucleotides, peptide conjugates, and antibody-linked delivery platforms, showing how chemistry is now designed hand-in-hand with biological intent.
Oligonucleotide chemistry is no longer just a supporting function...it’s the foundation of effective RNA drug design. Discover what these innovations mean for your company in the Oligonucleotide Chemistry, Manufacturing and Controls track.
2. Discovery Is Shifting from Screening to Platform-Driven Design
Traditional oligonucleotide discovery relied on iterative wet-lab screening and slow optimisation cycles. Today, discovery is becoming platform-driven, integrating AI, computational design, and translational modelling from the earliest stages.
Modern discovery platforms now enable:
- Rapid exploration of sequence and chemical space
- Predictive modelling of efficacy and safety
- Early identification of delivery-compatible candidates
- Reduced late-stage failures through smarter design
Across the discovery tracks, speakers show how AI-driven ligand design, receptor mapping, and integrated chemistry–biology workflows are accelerating the path from concept to clinic.
Discovery is no longer about finding one molecule...it’s about building systems that generate pipelines.
3. RNAi and Antisense Therapies Are Expanding Beyond the Liver
RNAi and antisense oligonucleotides have proven clinical success, but historically their reach was limited to the liver. That limitation is now being overcome.
New delivery platforms are unlocking extrahepatic tissues, including:
Muscle and adipose tissue for metabolic diseases
Kidney for systemic homeostasis
Lung for pulmonary disorders
Deep brain regions for neurodegenerative disease
CNS applications
Sessions across the delivery track showcase receptor-mediated shuttles, peptide ligands, LNP innovations, and antibody-oligonucleotide conjugates that are achieving tissue-specific delivery with real preclinical and clinical data.
Delivery is no longer the bottleneck...it’s becoming a competitive advantage. Learn more from the leaders in the field on how you can capitalise on the new wave in the Delivery of Macromolecules track.
4. Manufacturing and CMC Are Becoming Strategic Differentiators
As oligonucleotide pipelines expand, oligonucleotide synthesis and manufacturing have moved from operational concerns to strategic priorities.
The industry is now tackling:
Scale-up of complex chemistries
Solid-phase synthesis efficiency
Analytical characterisation of modified sequences
Cost of goods for chronic and large-population indications
Innovations in CMC are determining which programs advance and which stall. Sessions focused on manufacturing, purification, and CMC strategy highlight how companies are building scalable, reproducible, and regulator-ready processes from early development onward.
Manufacturing is no longer downstream...it’s shaping discovery decisions upstream. Have you got the right tools to make impactful decisions? The Oligonucleotide Chemistry, Manufacturing and Controls track will guide you into the next stage of manufacturing.
5. Integrated Platforms Are Defining the Next Generation of RNA Medicines
The most successful oligonucleotide programs no longer treat chemistry, discovery, delivery, and manufacturing as separate silos. Instead, they integrate them into end-to-end platforms.
These unified systems enable:
- Faster translation from discovery to clinic
- Early manufacturability assessment
- Smarter candidate prioritisation
- Platform scalability across multiple indications
Across the agenda, speakers show how integrated platforms are enabling precision, scalability, and speed - the three pillars required for oligonucleotide therapeutics to reach mainstream medicine.
The future of RNA therapeutics belongs to teams that build platforms, not just programs.
Why It Matters for Oligonucleotide Scientists and Drug Developers
Oligonucleotide therapeutics are no longer experimental. They are becoming a core pillar of modern drug development.
But success depends on solving chemistry, discovery, delivery, and manufacturing together, and doing so early. The sessions at TIDES USA 2026 show exactly how leading biotech and pharmaceutical teams are making that shift, sharing real data, real platforms, and real translational outcomes.
In 2026, success in RNA drug development won’t depend on a single breakthrough, but on how effectively teams integrate molecular design, delivery engineering, and scalable manufacturing into one coherent strategy.