Periodic Reporting for period 1 - GetRadi (Gene Therapy of Rare Diseases)
Reporting period: 2022-09-01 to 2024-08-31
A rare disease is a disease that affects less than 1 in 2 000 people. However, since more than 6000 rare diseases are known, approx. 300 Mio people are suffering from rare diseases worldwide, including 30 Mio in the EU alone. Not surprisingly, the EU recognised rare diseases as an important unmet health problem. Most of these rare diseases are caused by a genetic mutation and thus, a genetic therapy based on gene augmentation or, ideally, direct gene correction, is the only possibility to offer a permanent cure. Therefore, the overall goal of our network “Gene Therapy of Rare Diseases” (GetRadi) is to train 10 Early Stage Researchers (ESR) to become exceptional experts in gene therapy of rare diseases. In their research projects, the ESR will aim to overcome major technical challenges that still prevent the widespread use of somatic gene therapy in the clinic. All projects are embedded in a tight and synergistic academic-industrial collaboration to develop marketable products for the application of gene therapy. This GetRadi training will allow young scientists to spearhead future research efforts in gene therapy of rare diseases and thus increase the speed that desperately needed novel gene therapies are developed.
GetRadi has 3 scientific ojectives:
1. Develop and test new methods overcoming current limitations for transfer of genome editing tools into target cell
2. Develop and test innovative modifications or alternatives to classical CRISPR genome editing.
3. Establish models to quantify specific safety risks and develop methods and equipment to reduce gene therapy related risks
GetRadi has 3 scientific ojectives:
1. Develop and test new methods overcoming current limitations for transfer of genome editing tools into target cell
2. Develop and test innovative modifications or alternatives to classical CRISPR genome editing.
3. Establish models to quantify specific safety risks and develop methods and equipment to reduce gene therapy related risks
The GetRadi consortium established several cellular models for the rare diseases. These disease models will be corrected with different gene editing technologies including CRISPR gene editing and novel variants of it, which are less prone to adverse effects. In addition, novel regulators of the gene editing process have been identified that might be targets for increasing repair efficiency.
To introduce the gene editing tools into the target cells, GetRadi is testing and optimising different methodologies including electroporation, lipid nanoparticles, exosomes and adenoviral particles.
To increase the safety of gene therapy, variants of Cas9 with a reduced risk for immune reaction are investigated. Moreover, GetRadi is trying to perform gene editing of stem cells of rare disease patient by automated cell culturing equipment, in order optimize and standardize the therapy in compliance with good manufacturing practice.
GetRadi furthermore developed reporter cell lines and mice for testing of the efficiency and safety of in vivo and ex vivo gene therapy techniques, which includes gene editing tools, transfer of gene editing tools to target cells, sustained treatment success, and immune reactions.
Using the newly established tools and optimized methodologies described above, research of the GetRadi consortium will contribute to novel, more efficient, more safe, and less expensive therapy or rare diseases.
GetRadi aims to publish results from research on rare diseases in peer-reviewed articles. Seven review articles and one scientific article have so far been published, and more are to follow within the remaining project period.
To introduce the gene editing tools into the target cells, GetRadi is testing and optimising different methodologies including electroporation, lipid nanoparticles, exosomes and adenoviral particles.
To increase the safety of gene therapy, variants of Cas9 with a reduced risk for immune reaction are investigated. Moreover, GetRadi is trying to perform gene editing of stem cells of rare disease patient by automated cell culturing equipment, in order optimize and standardize the therapy in compliance with good manufacturing practice.
GetRadi furthermore developed reporter cell lines and mice for testing of the efficiency and safety of in vivo and ex vivo gene therapy techniques, which includes gene editing tools, transfer of gene editing tools to target cells, sustained treatment success, and immune reactions.
Using the newly established tools and optimized methodologies described above, research of the GetRadi consortium will contribute to novel, more efficient, more safe, and less expensive therapy or rare diseases.
GetRadi aims to publish results from research on rare diseases in peer-reviewed articles. Seven review articles and one scientific article have so far been published, and more are to follow within the remaining project period.
All scientific results described above are novel and therefore beyond the state of the art.