UNC advances RNAi potency platform

RNA interference, or RNAi, works by harnessing a natural cellular process to degrade specific messenger RNA strands before they can be translated into proteins. While the concept is well established and several RNAi drugs have reached the clinic, their effectiveness has often been limited by the challenge of delivering fragile RNA molecules intact to the right tissues and then releasing them from endosomal compartments once inside cells. UNC’s new platform addresses this bottleneck by combining chemical design with delivery engineering to amplify the biological impact of each dose.

According to researchers involved in the work, the technology focuses on enhancing endosomal escape, a stage where many RNAi candidates lose potency. After entering a cell, therapeutic RNA frequently becomes trapped in vesicles that ferry cargo for degradation. The UNC approach modifies carrier materials so they respond to the cellular environment, altering charge or structure in a way that disrupts the endosome and releases RNA into the cytoplasm. This mechanism allows a higher fraction of administered RNA to reach its target machinery.

Laboratory studies have shown that the platform can significantly increase gene-silencing efficiency at lower doses compared with conventional delivery systems. By improving potency, the technology could reduce the amount of RNA required for therapeutic effect, potentially lowering costs and minimising side effects linked to higher systemic exposure. Researchers say the platform has demonstrated consistent performance across different RNA sequences, suggesting broad applicability rather than a one-off optimisation for a single target.

The development comes as RNA-based medicines gain momentum across the biotechnology sector. Advances in messenger RNA vaccines have accelerated interest in nucleic-acid therapies more broadly, while RNAi continues to attract investment for its ability to address previously undruggable targets. However, delivery remains the primary hurdle separating promising laboratory results from reliable clinical outcomes. UNC’s work aligns with an industry-wide push to refine carriers, from lipid nanoparticles to polymer-based systems, that can safely and efficiently shuttle RNA into cells.

Beyond potency, the UNC platform emphasises modularity. Researchers describe a system that can be tuned for different tissues by adjusting chemical components, allowing developers to tailor delivery profiles without redesigning the core technology. Such flexibility is viewed as critical for translating RNAi into treatments for diverse conditions, ranging from rare genetic disorders to metabolic and inflammatory diseases.

Academic experts note that stronger delivery platforms could also widen the therapeutic window for RNAi. Enhanced intracellular release may enable intermittent dosing schedules or support combination therapies where RNAi is paired with small molecules or biologics. This could be particularly relevant in oncology and neurology, where sustained gene modulation is often required but systemic toxicity has constrained earlier RNA-based approaches.

Commercialisation pathways are already being explored. The university has a track record of translating nucleic-acid innovations through licensing and spin-out ventures, and the platform nature of the technology is likely to appeal to pharmaceutical partners seeking adaptable delivery solutions. Industry analysts say such partnerships are essential for scaling manufacturing, navigating regulatory pathways and validating safety in larger studies.

The timing is notable as regulators gain more experience evaluating RNA-based medicines. Clearer guidance on quality control, biodistribution and long-term effects has lowered some barriers that once slowed development. A delivery platform that can demonstrate reproducible potency improvements may benefit from this maturing regulatory environment, particularly if it can be integrated with established manufacturing processes.