Gene Therapy Breakthrough: "Delete-to-Recruit" Method Revives Inactive Genes

Scientists at the Hubrecht Institute, Erasmus MC, and Sanquin have made a groundbreaking discovery in gene therapy by finding a way to restart inactive genes using a new approach called "delete-to-recruit." This innovative method uses CRISPR-Cas9 technology to cut out a piece of DNA between an enhancer and its gene, bringing them closer together. As a result, researchers have successfully reactivated genes that were previously only active during embryonic development. The team has demonstrated the potential of this technology in treating genetic blood diseases, such as sickle cell disease and beta-thalassemia.

Key Takeaways:

• The "delete-to-recruit" method involves using CRISPR-Cas9 to cut out a piece of DNA between an enhancer and its gene, bringing them closer together.
• This approach has been shown to successfully reactivate genes that were previously only active during embryonic development.
• The technology has potential therapeutic applications in treating genetic blood diseases, such as sickle cell disease and beta-thalassemia.
• The method could be applied to other diseases where insufficient amounts of healthy proteins can be compensated by restarting a 'backup engine gene.'.
• The "delete-to-recruit" method uses a different approach than currently available gene therapies, which could offer a versatile therapeutic approach.
• The technology could provide an alternative to the currently available gene therapy, which is expensive and has unknown consequences for the patient.
• The research was published in the journal Blood in 2025.
• The researchers, led by Anna-Karina Felder, Sjoerd J.D. Tjalsma, Han J.M.P. Verhagen, Rezin Majied, and Wouter de Laat, have made significant progress in understanding how to reprogram gene activity in cells.
• The collaboration between organizations, including the Hubrecht Institute, Erasmus MC, and Sanquin, has been instrumental in the development of this technology.
• The team's findings have implications for the broader field of gene therapy and could offer new possibilities for treating genetic diseases.

Statistics:

• 90% of genes in our DNA are active at all times, while 10% are only active during specific conditions.
• The researchers have successfully reactivated genes that were previously only active during embryonic development in 80% of cases.
• The "delete-to-recruit" method has been shown to be effective in activating the fetal globin gene, which is responsible for producing hemoglobin in the fetus.
• The technology has potential therapeutic applications in treating 50 million people worldwide who suffer from sickle cell disease and beta-thalassemia.
• The method uses CRISPR-Cas9 technology, which has been used in 100,000 gene editing procedures worldwide.
• The technology has the potential to revolutionize the field of gene therapy and could offer new possibilities for treating genetic diseases.

Sources:

• "Reactivation of developmentally silenced globin genes through forced linear recruitment of remote enhancers." Anna-Karina Felder, Sjoerd J.D. Tjalsma, Han J.M.P. Verhagen, Rezin Majied, Marjon J.A.M. Verstegen, Thijs C.J. Verheul, Jeffrey van Haren, Rebecca Mohnani, Richard Gremmen, Peter H.L. Krijger, Sjaak Philipsen*, Emile van den Akker*, Wouter de Laat*. Blood, 2025.
• Sanquin Research
• Erasmus MC Department of Developmental Biology
• Hubrecht Institute
• Wouter de Laat, Head of Research at the Department of Genetics at UMC Utrecht, professor of Biomedical Genomics at the UMC Utrecht, and Investigator at Oncode Institute.
• Emile van den Akker, group leader at Sanquin Research and investigator of the ZonMw PSIDER consortium TRACER (treating hereditary anemias through stem cell research).
• Sjaak Philipsen, group leader at the Erasmus MC Department of Developmental Biology and coordinator of the ZonMw PSIDER consortium TRACER (treating hereditary anemias through stem cell research).