More than 7,000 rare diseases are known, around 80% of them genetic, and most have no approved therapy. Nucleic-acid medicines can address the root cause directly, but only if the carrier can be developed quickly and affordably for very small patient populations.
Rare disease is where nucleic-acid medicine has delivered its clearest successes. The first approved siRNA, patisiran, used a lipid nanoparticle to silence transthyretin in the liver for hereditary amyloidosis. Antisense therapy changed the outlook in spinal muscular atrophy, and the first CRISPR-based therapy was approved for sickle cell disease and beta-thalassaemia.
The liver is the easiest organ to reach, because standard lipid nanoparticles are naturally taken up by hepatocytes. That is why many rare-disease programmes target liver-made proteins first.
Muscle, lung, bone marrow and the CNS are much harder, and they hold many of the remaining unmet needs. Extra-hepatic delivery is the main focus of our rare-disease work.
Trials enrol few patients, so development cost per patient is high. Faster screening and reusable carrier platforms are what make these programmes viable.
Muscle, lung epithelium, haematopoietic stem cells and the CNS each need a dedicated carrier design, often with targeting ligands or local delivery.
Protein replacement by mRNA or knockdown by siRNA must be repeated for years, so the carrier must be biodegradable and well tolerated on chronic dosing.
Many rare diseases present in childhood, when the window to prevent irreversible damage is short and safety margins must be wider.
Nucleic-acid medicines for genetic disease follow three broad strategies, and each sets a different delivery target.
A carrier is defined by lipid or polymer identity, molar ratios, N/P ratio, buffer and mixing conditions. Changing one variable at a time across this space takes months.
We screen 40 or more compositions per cycle using microfluidic mixing and plate-based assays, then fit response models that predict the best region to test next.
Two or three cycles usually reach a lead formulation. Because the same platform carries different payloads, each new rare-disease programme starts from a validated carrier rather than from scratch.
Individualised antisense and editing therapies have now been designed for single patients with unique mutations, showing that bespoke genetic medicine can be built in months.
Regulators are developing platform pathways in which a carrier already characterised for one programme can be reused with a new sequence, so only the payload-specific data must be generated again.
| Payload | Rare-disease use | Delivery requirement |
|---|---|---|
| siRNA | Silences toxic proteins made in the liver | Hepatocyte uptake; repeat dosing |
| mRNA | Replaces missing enzymes or proteins | Chronic dosing; low immunogenicity |
| Antisense oligonucleotide | Corrects splicing, as in spinal muscular atrophy | Local or intrathecal delivery |
| CRISPR / base editor | One-time correction of the mutation | Co-delivery of mRNA and guide RNA |
Hepatic enzyme replacement carrier
Lead opt. · Undisclosed
We co-develop nanocarrier and biosensing programmes with pharma, biotech and academic groups — from target selection through GMP supply.
