Applied Biochemistry
Molecular Therapy

AG Fechner

Molecular Therapy

(Head: Dr. Henry Fechner)

Development of oncolytic coxsackie B3 viruses for the treatment of tumor diseases

Oncolytic viruses are promising new immunotherapeutics for cancer therapy. They infect cancer cells, replicate in them and destroy them, while replication in normal cells does not occur. At the same time, infection of tumor cells leads to a strong antiviral and antitumor immune response. In this project we focus on the development of oncolytic Coxsackie B3 viruses (CVB3) for the therapy of colorectal carcinoma. The starting point for this is CVB3 variants with strong oncolytic properties. An important focus is the safety of these viruses during application. For this purpose, specific sequences (microRNA target sequences) are used, which, when inserted into the CVB3 genome, prevent viral replication in healthy tissues such as the pancreas and the heart. Another important aspect is the investigation of the role of the immune system in the use of oncolytic CVB3. In addition, we are working on the development of tumor cell-specific adapted oncolytic CVB3. In vitro and in vivo (mouse models) studies on different tumor models (colorectal tumors, peritoneal carcinomatosis, xenograft and syngeneic models) are performed. The projects are funded by the TU internal funding project ProTuTec, the Berlin Cancer Society and the Wilhelm Sander Foundation.

Development of anti-adenoviral therapies for the treatment of severe systemic adenovirus infections in immunocompromised patients.

Adenovirus infections can lead to severe life-threatening infections in immunocompromised patients, such as organ transplant recipients. In this project, different approaches to antiviral therapy are being investigated. These include soluble viral receptor molecules that inhibit the docking sites of adenoviruses to target cells, siRNAs with which specific adenoviral genes are down-regulated, and new antiviral pharmaceuticals that block viral binding to target cells and viral replication. Another goal is to develop structurally modified anti-adenoviral siRNAs so that they can be effectively taken up by liver cells in vivo and remain stable in the cells for a long time. To this end, both in vitro and in vivo (hamster model) studies are being conducted. The project is funded by the German Research Foundation (DFG).

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