Genetics cannot explain type 2 diabetes, and epigenetics (i.e. chemical modifications of the DNA not affecting the genetic code) is expected to play a key role. The group of Professor Charlotte Ling in Malmö has identified a series of epigenetic differences between people with type 2 diabetes and people without the disease. It is not fully clear whether these changes are the cause or the consequence of the disease. To assess this, they need better methods to implement specific epigenetic changes and study the corresponding effects on cells. This study is an important step toward achieving this. In a proof-of-concept study, the authors deliver DNA plasmids coding for CRISPRi and show downregulation of the insulin gene in beta cells.
How would you describe this study?
“This study explores the possibility of achieving a change in insulin gene expression by delivering a set of certain DNA molecules (CRISPRi plasmids) to beta cells (insulin-producing cells in the pancreas) using nanoelectroporation. By utilising gentle electric pulses and nanoporous membranes, we were able to deliver custom-designed DNA molecules to beta cells, where they yielded a desired reduction of insulin gene expression. This is a first step towards successful epigenetic editing in beta cells using nanoelectroporation,” says Frida Ekstrand, one of the NanoLundian PhD students who defended her doctoral thesis last year.
Understanding more about the disease mechanisms is crucial for developing better and more targeted treatments.
“Epigenetics is thought to play a key role in type 2 diabetes. Enabling the changing of specific epigenetic signatures and studying the corresponding effect could expand our knowledge about the disease and potentially lead to new treatments. Type 2 diabetes is a group of diseases that affects the lives of over half a billion people every day, a number that is expected to increase further. Understanding more about the disease mechanisms is crucial for developing better and more targeted treatments. Our study suggests a new delivery method for studying these mechanisms in beta cells.”
Previously, delivering these large DNA molecules has only been achieved using empty virus shells.
“Using viruses poses several safety concerns, and they cannot be used for therapeutic purposes. We show in this study that we can alter gene expression using a non-viral method, which could open the possibility for therapeutic applications in type 2 diabetes,” says Frida Ekstrand.
What is the most important thing you have learned from this work?
“That a specific change in beta cell gene expression can be achieved using the non-viral method nanoelectroporation.”
Something surprising in the results was the significant effect that was observed:
“These cells express very high levels of insulin, and we estimate that we managed to affect about 25% of the cells. That a lower gene expression in only 25% of the cells, with the rest expressing normal levels of insulin, was significant was a bit surprising.”
The main conclusions of the study are that the authors showed that a significant downregulation of insulin gene expression through epigenetic modifications could be achieved by using nanoelectroporation.
“This is the first step towards assessing the causal effects of epigenetic marks in type 2 diabetes using nanotechnology. In the future, one could imagine targeting these effects for therapeutic purposes,” says Christelle Prinz, Professor of biophysics at the Division of solid state physics.
“I look forward to further developing this nanotechnology-based method for editing of specific epigenetic marks together with Professor Prinz’s group,” says Professor Charlotte Ling.
- The article “Nanopore Electroporation: A New Delivery Method Within the Field of Epigenetic Editing” in Small (2026)”
Authors: Frida Ekstrand, Sabrina Ruhrmann, Karl Bacos, Sabine Bartel, Pytrick Jellema, Marianne G. Rots, Charlotte Ling, Christelle N. Prinz. - Frida Ekstrand in the Lund University Research Portal
- Charlotte Ling in the Lund University Research Portal
- Christelle Prinz in the Lund University Research Portal