Stem cell gene editing by the new CRISPR/Cas-technique to be applied in the treatment of patients with immunodeficiencies
The research team behind the investment from Innovation Fund Denmark (photo: Private).
A number of hereditary primary immunodeficiencies increases the individual’s susceptibility to microorganisms and severe infectious diseases. Innovation Fund Denmark has now supported researchers from Aarhus University and Aarhus University Hospital with DKK 25 million (7 million Euros) to further develop the CRISPR/Cas technology and edit patient stem cells to cure these serious life threatening immunodeficiency diseases.
Knowledge of the genetic basis of immunodeficiencies has advanced dramatically over the past few years and new genetic sequencing technologies can now help identify the precise genetic defect causing disease.
With an investment of DKK 25 million from Innovation Fund Denmark, researchers from Aarhus University and Aarhus University Hospital will further develop the revolutionary CRISPR/Cas technique, which has made precise and effective editing of the human genome possible. The hope is to cure diseases by editing the genetic information in the stem cells of patients.
- The long term goal and perspective of this project is to help children with rare immunodeficiencies. Children who do not survive until adult age today, says Trine H. Mogensen, MD and Professor at Department of Infectious Diseases at Aarhus University Hospital and Department of Biomedicine at Aarhus University.
Professor at Department of Clinical Medicine, Aarhus University, Peter Hokland, has been involved in stem cell research for more than 30 years.
- With this novel center funded by Innovation Fund Denmark, it will become possible for a strong research team from Aarhus University and Aarhus University Hospital to launch a programme for the clinical implementation of the CRISPR/Cas technique.
- We hope to be able to obtain approval to treat the first patients within the first 5-year period. This is, however, only the first step in a broader perspective to develop the technology and obtain the necessary experience to treat other genetic diseases.. Facilities will be available in modern specialised laboratories at Aarhus University Hospital built by Aarhus University.
A new immune system
Researchers will isolate the patients' own stem cells and edit the genetic defect using a gene editing tool (a specific enzyme) to edit mutated genes in the genome.
The defective gene is then replaced by the correct genetic information, after which the stem cells can be re-introduced in the patient. When the patient's stem cells have edited the genes, they are transformed and given back to the patient.
In this way the defective immune system is replaced by immune cells formed by the edited stem cells, which will have the normal protective effect against infections.
Identification of an immune defect is performed by examining the cells of the immune system and sequencing the genetic information encoded within the genes of the immune system.
At present If an inherited gene defect is identified (inherited from the parents or as the cause of a new mutation), the disease may in this way be cured by transplantation of blood stem cells from the bone marrow of a healthy person.
However, it is a big challenge to find a suitable donor and often stem cell transplantation has severe complications. These complications and challenges can be avoided by editing the genetic defects by this new technology editing genes in the patient's own stem cells.
With this funding from Innovation Fund Denmark, a unique collaboration between Aarhus University and Aarhus University Hospital has been established. Rasmus Bak and Jacob Giehm Mikkelsen develop the genetic editing techniques at Aarhus University, whereas Trine H. Mogensen, Peter Hokland and Bjarne K. Møller are involved in identification, diagnostics, and treatment of patients with immunodeficiencies and transplantation of blood stem cells. The aim of the research group is to bring the CRISPR/Cas technique from the laboratory into clinical patient treatment.
Department of Clinical Medicine, Aarhus University, Peter Hokland, professor, Tel.: +45 20225333
Department of Infectious Diseases and Department of Biomedicine and Department of Clinical Medicine, Aarhus University Hospital and Aarhus University, Trine H. Mogensen, MD and Professor, Tel.: +45 20125280
Department of Clinical Immunology, Aarhus University Hospital, Bjarne K. Møller, Head Consultant and Clinical associate professor, Tel.: +45 78455000
Department of Biomedicine, Aarhus University, Jacob Giehm Mikkelsen, Professor, Tel.: +45 87167767
Aarhus Institute for Advanced Studies and Department of Biomedicine, Aarhus University, Rasmus Bak, Associate professor, Tel.: +45 87167272