GoKawiilShadi Farhangrazi (left) and Seyed Moein Moghimi.
Rare diseases, defined as occurring in fewer than 1 in 2,000 people worldwide, disproportionately affect children. Half of all rare-disease patients are children, and more than 30% do not reach their fifth birthday.
This is largely driven by the lack of treatment options. Although rare-disease treatments have accounted for at least half of all new drug and biologic approvals by the US Food and Drug Administration (FDA) over the past five years, fewer than 5% of rare diseases have an approved therapy. Delivering gene-editing therapies to the brain, where most paediatric rare diseases affect the nervous system, is key to improving prognoses. But it is one of the biggest challenges in drug delivery today.
Nature Index 2026 Nanoscience and nanotechnology
Viral vectors, which are modified viruses that are used to deliver genetic material into cells, have been the primary vehicles for gene therapies. Despite billions of dollars in investment, however, many have fallen short of early expectations. Studies have revealed significant limitations1, including a relatively small payload capacity that restricts the delivery of some gene‑editing systems, and trouble crossing the blood–brain barrier — a protective layer of cells that controls what substances pass from the blood into the brain.
There are significant safety concerns with using viral vectors. Sending viruses through the bloodstream requires very high doses to cross the blood–brain barrier, which increases the risk of harmful side effects such as organ damage and inflammation of the brain and spinal cord2. Direct injection into the brain avoids the blood–brain barrier, but is still risky and can only target small areas for treatment.
Viral vectors are not a good option for children with rare diseases. We believe that nanotechnology offers a promising alternative.
Lipid nanoparticles have shown encouraging results as vehicles for gene-editing systems. Last year, a major milestone in paediatric rare-disease care was achieved when a team from the Children’s Hospital of Philadelphia and the University of Pennsylvania used lipid nanoparticles to deliver gene-editing tools that corrected a liver mutation in a young patient, offering an alternative to transplant3.
This was not the first time that lipid nanoparticles have been used to deliver genetic material into cells (mRNA COVID-19 vaccines rely on the same technology), but it demonstrated a new application in delivering gene-editing tools to correct disease-causing mutations in young patients.
There are important caveats. Like viral vectors, lipid nanoparticle-based systems come with safety concerns4. And they also mostly end up in the liver, which makes targeting the brain very difficult. Yet these challenges should not obscure the broader opportunity: advances in nanotechnology-based drug delivery are still in their infancy, and sustained momentum in this field will be crucial to unlocking new therapies for children who currently lack options.
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