Main Conference – Day 1 - CET (Central European Time, GMT+01:00)
- Developing self-assembling siRNA therapeutics designed for effective and targeted delivery via inhalation to treat respiratory diseases.
- Optimizing siRNA formulations to ensure stability, efficient pulmonary uptake, and minimal off-target effects.
- Demonstrating safety and therapeutic efficacy through advanced preclinical models of respiratory disease
- Philippe Vollmer Barbosa - Project Manager, Fraunhofer
Emerging extra‑hepatic delivery platforms are extending the therapeutic reach of oligonucleotides by enabling selective tissue and cell targeting. Novel chemistries are enhancing molecular stability, cellular uptake and potency, while minimising off‑target effects. Bioconjugation strategies, including transferrin receptor–mediated targeting and antibody–oligonucleotide conjugates, are promising new approaches. Together, these innovations are accelerating the development of safer, more effective oligonucleotide therapeutics
- Nick Lench - Executive Director, Nucleic Acid Therapy Accelerator
RNA nanotherapeutics have risen to prominence following recent clinical successes, yet their broader potential remains constrained by liver biased biodistribution, a restricted cell tropism, and inadequate cell delivery due to poor endosomal escape. To gain a deeper understanding of the many complex in-vivo mechanisms and to identify the optimal drug characteristics needed to navigate these processes, we must devise a robust platform of assays and models capable of evaluating each relevant property of the drug. Establishing such a comprehensive and predictive preclinical cascade is essential to support the rational design and optimisation of next-generation RNA delivery vehicles, ultimately accelerating the future success of RNA therapeutics. To address this, five UK partner organisations have established the Intracellular Drug Delivery Centre (IDDC), creating a centre of excellence for lipid nanoparticle (LNP) innovation. The centre integrates high-throughput screening of novel lipid chemistries and formulation with mechanistic assessment of key formulations in cell models and small mammals. Our data from thousands of LNP formulations reveals the complexity of their structure-activity relationships, allowing us to map specific biological functions to distinct LNP components. Furthermore, we find that exceptions to the internalisation rupture-expression model highlight as yet unappreciated biological intricacies that control LNP functionality in target cells. Altogether, this work has advanced the rational design of next-generation RNA nanotherapeutics and revealed principles to guide the design of future LNPs.
- Aadarash Zia - Senior Scientist - Drug Delivery, Medicines Discovery Catapult
- Cell-free RNAs (cfRNAs), stabilized by extracellular vesicles (EVs), lipoproteins, and RNA-binding proteins (RBPs), are emerging as key players in RNA therapeutics and biomarker research, with a focus on their role in cell-to-cell communication.
- Recent findings emphasize the importance of RBPs in cfRNA biology, highlighting their potential to enhance stability, specificity, and targeted uptake for next-generation RNA therapeutics. cfRNAs also show promise as non-invasive biomarkers for real-time monitoring of therapeutic efficacy and optimizing personalized treatments.
- Integrating cfRNA discoveries into RNA therapeutic pipelines offers the potential to advance individualized treatment strategies, improve patient outcomes, and set new standards in RNA-based medicine.
- Bogdan Rivoal - CEO, NeXendia