RNA-medicine developer miRecule is teaming up with a Brazilian arm of pharmaceutical group EMS to tackle one of the field’s biggest limitations: getting RNA drugs to reach tissues beyond the liver.
The collaboration pairs miRecule’s NAVIgGator platform for designing precision RNA medicines with the peptide-engineering capabilities of Rio Biofarma Brasil (RBBL), an EMS subsidiary. The goal is peptide-mediated delivery.
Why RNA drugs reach the liver so easily
The liver’s dominance in this field is a consequence of anatomy and chemistry rather than deliberate targeting.
The organ filters everything in the bloodstream by design, and its blood vessels are unusually permeable — lined with gaps allowing large molecules to pass out and reach liver cells directly. Most tissues have tight vessel walls that exclude anything of that size.
Liver cells also carry a receptor that takes up particles bearing a specific sugar structure, and attaching that sugar to an RNA molecule delivers it efficiently. The mechanism is well understood, works reliably, and underpins essentially every approved RNA drug.
Nothing equivalent exists for most other organs. Muscle has been reached with difficulty at high doses, and beyond that the field has largely been stuck.
What the delivery problem actually involves
Reaching a tissue is only the first of several barriers.
An RNA molecule in the bloodstream is degraded by enzymes within minutes unless chemically modified, and it is filtered out by the kidneys because of its size and charge. It must then leave the circulation, cross the cell membrane — which excludes large negatively charged molecules — and, having entered by uptake into a vesicle, escape that vesicle before it fuses with a lysosome and is destroyed.
That last step, endosomal escape, is the one that defeats most delivery approaches. Molecules routinely enter cells and never reach the cytoplasm where they would work.
Why peptides
Peptides — short chains of amino acids — are attractive escorts for reasons specific to these obstacles.
They can be designed to bind receptors expressed preferentially on particular cell types, providing targeting the liver receptor provides by accident. Certain peptide sequences also disrupt membranes under the acidic conditions inside an endosome, which addresses the escape problem directly.
They are chemically synthesised, so they can be produced consistently and modified systematically. And being made of amino acids, they degrade into ordinary metabolic products rather than accumulating.
The difficulty is that these properties trade against one another: a peptide effective at disrupting membranes may disrupt them indiscriminately, and one highly specific in binding may bind too tightly to release its cargo.
How the deal is structured
miRecule will develop the oligonucleotide payloads for up to three targets, while RBBL will manufacture at its facility in Brazil.
RBBL is making an equity investment in miRecule to support the work and the company’s neuromuscular-disease assets; the resulting technology will be jointly owned. Other terms were not disclosed.
Joint ownership is the notable term. It is less common than licensing and reflects a genuine co-development arrangement rather than one party contracting services from the other — appropriate where the value created is a platform capability rather than a specific product.
Why neuromuscular disease
The focus is consistent with the delivery problem being solved. Muscle is among the tissues RNA drugs reach poorly, and it is a large, distributed target requiring substantial drug quantities to affect meaningfully.
Several neuromuscular conditions are caused by single well-characterised genetic defects, so the therapeutic logic is settled and delivery is the remaining obstacle — which makes them the natural first application for a delivery advance.
Where it stands
“Working alongside an organisation with the scale, scientific commitment, manufacturing expertise, and global reputation of EMS-RBBL strengthens our ability to bring transformative technologies closer to patients,” miRecule chief executive Anthony Saleh said.
Why lipid nanoparticles did not solve this
The other major delivery technology in RNA medicine is worth contrasting, because its limits explain why peptide approaches are still being pursued.
Lipid nanoparticles encase RNA in a fatty shell that protects it and helps it enter cells, and they are what made mRNA vaccines possible. They work well and are proven at enormous scale.
Their targeting, however, is largely determined by where they naturally accumulate. Injected into the bloodstream they concentrate in the liver, for the same anatomical reasons that favour every other systemic approach. Injected into muscle they stay largely local, which suits a vaccine and not a systemic therapy.
Considerable work has gone into altering that distribution by changing lipid composition or attaching targeting molecules, with real but incomplete progress toward tissues such as lung and spleen.
Peptide conjugates take a different route: rather than packaging RNA in a particle whose destination is governed by particle behaviour, they attach it directly to a molecule chosen for where it binds. The construct is smaller and its targeting is a design choice rather than a physical property — which is the appeal, and it brings its own problem of getting enough cargo delivered per molecule.
Approaches widening the reach of RNA drugs are a major focus of the field, and many have been attempted. The programmes here remain early-stage. Business news, not investment or medical advice.