Magnets instead of viruses as gene vectors
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Gene therapy is considered the hope for many previously incurable diseases. But the viruses used so far as gene shuttles proved to be too risky. Now scientists want to transport genes into body cells using nanoparticles and magnetic fields.
Risk from viral gene shuttles
In many diseases, the hematopoietic cells are impaired. This is the case, for example, with the rare hereditary diseases SCID-X1 and ADA-SCID. The patients, also known as "bubble kids", suffer from a disorder of the immune system. Any infection can be fatal. With the help of viruses, physicians are able to introduce genes into the blood-forming cells of the "bubble kids" and thus permanently correct the defective genetic material.
However, this viral gene therapy poses dangers because the virus genes can lead to serious complications. In a study of eleven "bubble kids", eight children were cured, but three children developed uncontrolled proliferation of the treated blood cells. This problem was caused by components of the viral gene sheaths used, not by the gene used for therapy. In other diseases, such as cancer, possible side effects of viral gene transfer are a hurdle to otherwise promising gene therapy. But how can genes be introduced into human genetic material without the practical "viral ferries"?
Magnets instead of virus
"If our project succeeds, it can be very simple, " explains Dr. Christian Plank, biochemist at the Institute of Experimental Oncology and Therapy Research of the Klinikum rechts der Isar, TU München. He has assembled an international team of specialists with 13 working groups from Europe, Israel and the USA, who are researching new gene vectors with the help of EU funding. "One connects gene molecules with magnetic nanoparticles and then leads them with a magnetic field into the target cells." Behind this "simple" idea lies decades of research work. As early as the 1960s, physicians developed methods for transporting medicines to the right place in the body via magnets.
This process, called "magnetic drug targeting", ie magnetic drug therapy, was followed up intensively and was also used in cancer treatment in humans in the mid-1990s. A medical team of the Berlin Charité dared the step and brought anti-tumor agents by magnetic technology in the cancerous organs. The so-called "nanomagnetomedicine" was successful. The biochemist Plank learned about it and continued to grasp the idea: "What works for small drugs, but should also for nucleic acids - the building blocks of the genes - work." Display
This laid the foundation for gene therapy that works without any viral components. In 2000, Plank began to develop the method known as magnetofection at the Institute of Experimental Oncology, and was successful after only a few months. But before the technology is so well-established and safe that it can be used in humans, a series of investigations are still pending.
With umbilical cord blood and nanoparticles
Each of the 13 working groups involved in the EU project carries out one of these studies. The task of Plank's research group is to link two crucial processes: First, the production of blood-forming cells (hematopoietic stem cells) from umbilical cord blood using magnetic nanoparticles. Second, the linking of these stem cells with gene sequences - also using magnetic nanoparticles. When these two techniques come together, magnetic cell separation and magnetic gene transfer outside the body, scientists can gain "healthy" bloodstream cells in a fast and controlled manner.
If these gene therapy treated stem cells are then transferred to the blood of patients such as the "Bubble Kids" mentioned above, the new blood cells could replace the genetically defective cells. Whether this last step can succeed, examine the other working groups of the international project. "We have reason to hope that it could work, " says Plank cautiously. His vision for the future: "In three to five years, one form of this new method could be used in the Klinikum rechts der Isar in cancer therapy."
(TU Munich, July 20, 2005 - NPO)