Gene therapies are widely regarded as one of the great hopes of modern medicine. They promise to treat diseases at their root by repairing or replacing faulty genes. Yet a central challenge remains unsolved: how to deliver therapeutic genes safely and precisely to the right cells. The most common methods rely on viruses or synthetic fat particles known as lipid nanoparticles (LNPs). Both approaches have their limitations. Viral vectors can trigger immune reactions, and lipid nanoparticles almost invariably end up in the liver. Organs such as the kidneys, the lungs, and the skin remain difficult to reach.
From Power Plant to Gene Shuttle
This is where Zurich-based biotech startup cellvie comes in. The company is pursuing a surprising idea: mitochondria — the powerhouses of our cells — could serve as biological delivery vehicles for genetic therapies. Mitochondria are tiny structures found in almost every human cell, responsible for producing energy. They carry their own DNA and are capable of traveling from cell to cell. These are precisely the properties cellvie is looking to harness. The concept: mitochondria are loaded with additional genetic information — so-called plasmids — transforming the cell's power plant into a biological gene shuttle capable of delivering its cargo directly into target cells.
"Mitochondria are significantly larger than existing delivery vehicles such as lipid nanoparticles or viral vectors. This means they can carry much larger DNA fragments and transport them into organs that are difficult to reach with established approaches. Mitochondria could therefore offer a solution for genetic defects that have so far been untreatable." — Martijn Brugman, CTO, cellvie
But how do loaded mitochondria actually enter target cells? Like synthetic nanoparticles, they are taken up by cells through endocytosis. However, unlike synthetic particles, the body recognizes them as beneficial components. This allows them to more efficiently overcome the so-called endosomal barrier, where a large portion of LNP cargo is typically lost. Repeated treatments are also feasible with mitochondria, as they do not trigger significant immune responses.
Kidney, Lung, and Skin: New Pathways to Hard-to-Reach Organs
The approach is particularly exciting for organs that have so far been largely beyond the reach of gene therapies. Hereditary kidney diseases, cystic fibrosis, and genetic skin conditions are notoriously difficult to treat because conventional delivery methods barely reach these tissues. Mitochondria could, for the first time, provide access. Early studies suggest they can be introduced into solid organs in a targeted manner using minimally invasive procedures.
"What we could only hope for a few years ago is today a tangible prospect. With our mitochondrial constructs, we have repeatedly and successfully transfected kidney, lung, and skin in vivo — using both RNA and DNA constructs. We have observed expression even after 28 days, and single-cell sequencing has confirmed that mitochondria are able to cross the endothelial layer." — Alexander Schueller, CEO, cellvie
In doing so, cellvie could close a gap that has persisted in gene therapy for years: enabling effective treatments for organs beyond the liver — including for large genetic constructs that LNPs or viral vectors have so far been unable to deliver into cells.
First Application: Treating Epidermolysis Bullosa
cellvie plans to bring its gene vector technology into clinical use for the first time in the treatment of epidermolysis bullosa (EB), a rare hereditary disease in which even minor mechanical stress causes severe skin injuries. Affected individuals suffer from chronic wounds, persistent pain, and a significantly elevated risk of infection. The focus is on the targeted delivery of a functional COL7A1 plasmid into skin cells to address the underlying genetic defect. Early preclinical data are promising and are intended to pave the way for near-term clinical translation.
Swiss Funding for a Pioneer Technology
The broader recognition of this research is reflected in funding from Innosuisse, the Swiss Innovation Agency. In 2024, cellvie received support through the competitive Swiss Innovation Project program to advance the development of mitochondrial gene therapy vectors. The grant underscores the importance of such platform technologies for Switzerland as a hub for biotechnology. In Switzerland, mitochondrial therapies would likely be classified as biological medicinal products and fall under the Therapeutic Products Act. The precise regulatory classification remains open, however, as mitochondria used as gene therapy delivery vehicles represent an entirely new product category.
Outlook
The path to clinical application is still long. But the potential is enormous: if the mitochondrial approach proves its worth, it could make gene therapies safer, more broadly applicable, and independent of viral systems. For patients with diseases affecting hard-to-reach organs, that would be a breakthrough. And for Switzerland as a research and innovation hub, it would be further proof that the country is not only conducting cutting-edge science, but actively shaping the future of therapeutic medicine.
References
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