The road to applied gene therapy is long: not only must a genetic ‘repair kit’ be developed for the disease-causing defect in the patient's genome and safely delivered to the treatment site in the body – packaged in artificially produced viruses – but the loaded viruses must also be produced in sufficient quantities. Thanks to a generous donation from the Dietmar Hopp Foundation, the team led by Patrick Most, Professor of Molecular and Translational Cardiology at Heidelberg University's Medical Faculty, has now come significantly closer to this important step: the foundation is providing 1.2 million euros to support the establishment and operation of a highly complex production unit for therapeutic viruses. With the new equipment, these can be produced in larger quantities than before, purified and checked for quality in the Department of Cardiology, Angiology and Pneumology at the UKHD.
Gene therapies have the potential to make previously incurable diseases treatable by correcting disease-causing genetic mutations. To do this, intact copies of the damaged or blocked genes are introduced into the affected cells. Thanks to the ‘repair genes,’ the cells can resume their disrupted functions, at least in part. Viruses serve as transporters for the repair genes: these ‘gene taxis’ dock onto the cells and transfer the genetic material. So-called adeno-associated viruses (AAV) are used for this purpose, which have long been used in medical research.
More than 15 years of research into gene therapy for chronic heart failure
AAV-based gene therapies are already being used successfully to treat certain diseases of the central nervous system, the eye and the liver. To enable patients with chronic heart failure to benefit from this form of therapy in the near future, the research group led by Dr Julia Ritterhoff and Prof. Patrick Most, Section of Molecular and Translational Cardiology at the UKHD, has been conducting intensive research into suitable ‘repair genes’ and gene taxis for more than 15 years and has successfully tested the procedure on mice. However, before it can be used in humans for the first time, the new gene therapy must first be proven safe and effective in a large animal model, namely pigs.
However, the previous production capacities for the viruses were not sufficient for this, as many times the previous quantity is now required. With the new equipment, production can be carried out in compliance with regulatory requirements and development processes. The production unit includes heatable fermenters that can hold up to 200 litres of nutrient medium for cell and virus cultivation, a purification system and devices that measure whether a sufficient number of viruses have taken up the therapeutic genes.
Preliminary work for industrial production should accelerate the transition to application
‘Such production units for gene therapies do not yet exist in the university sector in Germany. This will enable us to develop the optimal production conditions and thus lay the groundwork for industrial manufacturing,’ says Prof. Most. Over the next two to three years, the aim is to match the quality of biotechnological manufacturing processes. ‘We hope this will significantly accelerate the move to clinical application and initiate a seamless translation process,’ says Dr. Ritterhoff, co-head of the working group. Subsequently, the AAV production unit will also be made available to other working groups at Heidelberg Medical Faculty for the development of new gene therapies.
Research into gene therapies has been a focus of the Department of Cardiology, Angiology and Pneumology at UKHD and the federally funded German Centre for Cardiovascular Research (DZHK) for many years. ‘Thanks to the generous support of the Dietmar Hopp Foundation, we can further expand our pioneering role in the field of gene therapies, for example within the framework of the National Initiative for Gene and Cell Therapies,’ says Prof. Norbert Frey, Medical Director of the department.
Milestone on the road to safe gene therapy: therapeutic viruses with a shipping address
An article by the authors Most, Ritterhoff and Frey was recently published in the renowned journal Circulation. In it, the scientists describe a novel, heart-specific AA virus that recognises heart muscle cells with high precision. This allows the viruses to be administered intravenously into the bloodstream and still find their target safely. This can reduce unwanted effects in other organs. ‘With its heart specificity, the new virus prototype is far superior to the AAV vectors clinically tested to date and forms the basis for a new generation of gene therapies,’ says Prof. Most.
Original publication: Zeissler D, et al., Novel Human Heart-Derived Natural Adeno-Associated Virus Capsid Combines Cardiospecificity With Cardiotropism In Vivo, Circulation, August 2025.
Source: Press release Heidelberg University Hospital
