King's College London

Nanoneedles are microscopic, cone-shaped structures made of silicon. When placed in contact with cells, they gently "inject" therapeutic molecules into the cell interior, bypassing many of the challenges faced by conventional delivery methods like viruses or chemical carriers. In this study, nanoneedles were used to deliver an adenine base editor – a CRISPR-based gene-editing technology – into skin cells from patients with epidermolysis bullosa (EB).

For people with EB, a specific mutation in the collagen VII gene prevents the skin from producing type VII collagen, a critical protein that holds skin layers together. The work was conducted by Dr. Salman Mustfa and Ms. Marija Dimitrievska, alongside a wider team of researchers from King’s College London and the Polish Academy of Sciences, led by Dr. Ciro Chiappini in collaboration with Prof. John McGrath and Dr. Joanna Jackow from St. John’s Institute of Dermatology.

The team achieved highly precise correction of the mutation, restoring healthy gene function in the treated cells. Importantly, the nanoneedles did so without harming the cells or causing unwanted genetic changes elsewhere—one of the key concerns with many gene-editing approaches.

“What’s exciting,” explains Dr. Chiappini, “is that nanoneedles offer a gentle and highly efficient way to deliver gene-editing tools into patient cells. This approach avoids the toxicity and immune responses often associated with conventional delivery methods. It could transform genetic engineering for cell therapies.”

The edited cells resumed production of collagen VII and showed improved attachment properties—an important functional improvement for cells destined for therapeutic use.

This breakthrough demonstrates, for the first time, that nanoneedles can safely and effectively deliver base editors into patient-derived cells to correct a genetic defect in a clinically relevant disease model. The study lays crucial groundwork for using nanoneedle technology in manufacturing gene-edited cells for future therapies.