Published: 3.4.2025
Text: Diego Balboa
Editing: Viestintätoimisto Jokiranta Oy

Diabetes affects more than 550 million people worldwide. Current treatments focus mainly on managing blood sugar levels rather than resolving the causes of the disease. However, recent advances in genome editing technologies offer a new avenue for correcting the genetic defects responsible for certain forms of diabetes. Scientists are now using genome editing tools to correct mutations causing neonatal diabetes. The aim is to find new long-term treatment options.

The treatment of monogenic diabetes is challenging

Diabetes is usually caused by the autoimmune destruction (Type 1) or dysfunction (Type 2) of the pancreatic beta cells, the only source of insulin in the body. In addition, there are some rare forms of diabetes, known as monogenic diabetes, that are caused by single gene mutations. One of these forms, Permanent Neonatal Diabetes Mellitus (PNDM), appears in newborns due to genetic defects affecting pancreatic beta-cell insulin production and secretion.

Currently, patients with neonatal diabetes require lifelong insulin therapy. However, it is not a cure but a management strategy. A better approach would be to directly correct the genetic mutation that causes their diabetes, thereby restoring normal insulin production in the patient’s own cells. This is where CRISPR genome editing comes into play.

How can CRISPR genome editing help?

CRISPR genome editing is an advanced technique that allows scientists to precisely change individual DNA bases in the cell’s genome. Recent advances in genome editing provide unprecedented opportunities to correct genetic defects safely. Unlike traditional CRISPR-Cas9, which induces cuts in the cells’ DNA, base and prime genome editing allows precise substitutions without compromising genomic integrity. Preclinical studies have demonstrated the potential of base and prime editing for correcting congenital blindness, liver enzyme defects and immunodeficiency, making it a promising strategy for monogenic diabetes.

To test this approach, we are using stem cell-derived islets (SC-islets), which are lab-grown pancreatic cells that mimic natural islets. By implanting these SC-islets into animal models and applying CRISPR genome editing, researchers can evaluate the effectiveness of genetic correction in a living system. If successful, this technique could pave the way for clinical applications, offering a potential treatment for neonatal diabetes.

Experimental models accelerate the development of new treatments  

Experimental models that elucidate diabetes mechanisms are critical for developing improved therapies. CRISPR genome editing is revolutionising medicine. Our goal is to optimise it as a tool to restore pancreatic islet function. By identifying the best strategies for in vitro and in vivo mutation correction, we aim to accelerate the development of genome-editing-based diabetes treatments.

The widespread prevalence of diabetes motivates the urgency to expand therapeutic options. Our research is focused on translating stem cell and genome editing research into therapeutic solutions. In the long term, genome-editing therapies could significantly reduce the societal and economic burden of diabetes, thereby benefiting millions worldwide.

 

 

PhD Diego Balboa is a group leader at the Faculty of Medicine, University of Helsinki. His research involves genome editing tools and stem cells to understand the molecular mechanisms involved in pancreatic islet development and diabetes.

 

 

 

Main image: Pancreatic islet cells derived from human pluripotent stem cells. Credit: Diego Balboa

Links:

• https://www.nature.com/articles/s41587-022-01271-9
• https://www.duodecimlehti.fi/duo16763
• https://www.nature.com/articles/d41586-024-04102-w
• https://1in6b.com/