Jump to page content

Some 8,000 different diseases are caused by an error in a single gene. This error results either in the gene not being read at all and therefore not producing the protein it encodes, or in the protein being produced in the wrong form or quantity.

Scientists have long dreamed of being able to correct these individual errors with pinpoint accuracy. With the help of gene transporters known as shuttle vectors, it is possible to replace faulty genes with the correct version. However, it is of utmost importance that the correct gene ends up in the right place in the genome, otherwise serious side effects can occur.

Keeping tabs on the therapeutic gene

To check this in advance, a team led by Christof von Kalle and Manfred Schmidt developed several methods to track and monitor newly introduced genes in the genome of the treated cells, including a method known as LAM-PCR. This amplifies the DNA sequences flanking the therapeutic gene, thus allowing them to be carefully analyzed. Scientists can then use this information to determine the risk of a newly developed gene therapy vector settling in the immediate vicinity of dormant cancer genes and inadvertently activating them.

“Our method was first used clinically as an emergency response in the first gene therapy studies when, unfortunately, serious problems started to occur,” von Kalle recounts. “Back in the nineties, children with severe immunodeficiency received gene therapy that initially cured their disease. Instead of having to stay quarantined in a hospital room, they were once again free to play with the other kids and run around in the playground. However, some of them experienced severe side effects in addition to this phenomenal success: the therapeutic cells mutated into cancer cells and the children developed leukemia.” The French doctor performing the therapy called in von Kalle and Schmidt’s team to examine the children’s genetically modified cells. The team discovered that the shuttle vector had inserted the therapeutic gene right next to a cancer gene that it had then activated. Following this discovery, the gene therapy study was suspended and von Kalle and Schmidt’s methods were used to develop and test new-and-improved vectors.

Tracking modified cells in the body

“Today, of course, gene therapy has progressed a lot and new shuttle vectors insert the therapeutic gene with far greater precision,” von Kalle reports. “Another tool, CRISPR-Cas, is also becoming increasingly accurate, allowing us to cut out only the specific faulty site within a gene and replace it with the correct letters or gene segments.”

Today, gene therapy vectors are often used in the treatment of cancer. In so-called CAR T-cell therapy, for example, cancer patients receive genetically modified immune cells that can seek out and destroy cancer cells. However, these vectors and the cells undergoing treatment also need to be monitored throughout the various stages of development of new gene therapies. “Even after the therapy has been administered, we can track whether the cells in the patient’s body are doing what they are supposed to, whether they are killing the cancer cells, whether they are maybe multiplying too much, or whether they are disappearing,” von Kalle adds. “All of this improves the safety and efficacy of these therapies.” The safety procedure developed by von Kalle and Schmidt is now used in many gene therapy studies worldwide. The company GeneWerk, which the scientists co-founded, works together with international gene therapy developers in the public and private sectors.

Focusing on gene therapy at the BIH

Professor Christopher Baum, Chair of the BIH Board of Directors and Chief Translational Research Officer of Charité, congratulates von Kalle on the Outstanding Achievement Award: “As a physician and scientist, Christof von Kalle has always committed himself with the greatest dedication and outstanding success to the development of new, improved therapies that help restore patients’ health. As the current Director of the Charité-BIH Clinical Study Center, he is not only committed to the safety of innovative approaches to gene therapy, but also contributes significantly to the success of many other targeted and personalized treatment methods.”

But the occasion is also tinged with sadness for Christof von Kalle, as he cannot accept the prize together with his long-time research partner and friend Dr. Manfred Schmidt, who died far too young just a few months ago. “I would have loved to receive this prize together with Manfred, because we developed the method together. I am very pleased that his family will be present in Edinburgh. We will be dedicating the award to his memory.”


  • Zwei Männer sitzen an einem Schreibtisch und schauen auf einen Comupter-Bildschirm. Ein Mann in einem blauen Kittel zeigt auf den Screen, wo eine medizinische Bildaufnahme zu sehen ist.

    Clinical Study Center (CSC)

    The Clinical Study Center (CSC) is the cross-campus platform for clinical studies. It consists of the Clinical Trial Office (CSC-CTO) and the clinic-based Clinical Trial Unit (CSC-CTU).

    Read more

Pressekontakt / Press contact

Katharina Kalhoff: +49 1515 7579574

Ole Kamm: +49 1522 5610126

Contact information