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CRISPR/Cas9 technology to inactivate cancer mutations

Technische Universität Dresden

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Credit: Stephan Wiegand, TU Dresden

CRISPR/Cas9 is likely one of the most revolutionary tools in biotechnology, with tremendous implications for a broad range of biological and medical disciplines. As programmable scissors this technology allows cleavage of DNA at predefined sites in the genome of cells. Now researchers from the National Center for Tumor Disease (NCT) Dresden, the German Consortium ortium for Translational Cancer Research (DKTK) and the Medical Faculty of the TU Dresden have found a way to utilize the technology to diagnose and inactivate cancer mutations, thereby accelerating cancer research.

"Mutations in cancer cells are identified at increasing speed through next generation sequencing, but we mostly do not know, which of these mutations are actually driving the disease and which ones are rather benign " said Frank Buchholz, head of the study that appeared in the latest addition of the Journal of the National Cancer Institute (JNCI). The authors first analyzed how many of the more than 500,000 reported cancer mutations could theoretically be targeted and found that >80% of the mutations could be cleaved with the currently most popular CRISPR/Cas9 system. The research group then demonstrated that they could specifically cleave a panel of common cancer mutations without significantly targeting the healthy, wildtype alleles. Moreover, expression of Cas9 together with the cancer-specific guide (g)RNAs was able to unmask mutations that drive cell growth and viability in cancer cell lines. Buchholz points out: "This is an important advance, because we can now rapidly separate driver from passenger mutations. This is currently a bottleneck in cancer research. Because each cancer shows a specific combination of many mutations, this scientific approach could improve cancer diagnostics as mutations that promote cancer growth could be specifically identified. Based on the obtained results an individualized therapy could be initiated.

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Publication: Gebler et al., Inactivation of cancer mutations utilizing CRISPR/Cas9. JNCI
DOI: 10.1093/jnci/djw183
http://jnci.oxfordjournals.org/content/109/1/djw183.full

Information about the National Center for Tumor Diseases (NCT) Dresden

The National Center for Tumor Diseases (NCT) Dresden is a joint institution of the German Cancer Research Center, the University Hospital Carl Gustav Carus Dresden, the Medical Faculty of the TU Dresden and the Helmholtz-Zentrum Dresden-Rossendorf and is being established as partner site of the NCT Heidelberg since 2015. It is part of the NCT strategy to link basic research and patient care as closely as possible. Hence, cancer patients in Dresden and Heidelberg can be treated on the basis of the latest state of scientific knowledge. At the same time scientists of the NCT highly benefit from the immediate vicinity of laboratories and clinical institutions and receive important input for their research. The joint goal of the partner sites is to develop the NCT to an international excellence center in patient-oriented cancer research.

Information about German Cancer Consortium (DKTK)

The German Cancer Consortium (DKTK) builds a strong, long-term, institutional structure between the German Cancer Research Center (DKFZ) and universities and university hospitals all over Germany specially designated to clinical oriented cancer research.

As DKTK's core center the DKFZ works together with research institutions and hospitals in Berlin, Dresden, Essen/Düsseldorf, Frankfurt/Mainz, Freiburg, Munich, Heidelberg and Tübingen to create the best possible conditions for clinical cancer research. The consortium promotes interdisciplinary research at the interface between basic research and clinical research, as well as clinical trials for innovative treatments and diagnostic methods. Another key focus of the consortium's work is on developing research platforms to speed up the application of personalized cancer treatments and to improve the diagnosis and prevention of cancer. The German Cancer Consortium (DKTK) is a joint long-term initiative involving the German Federal Ministry of Education and Research (BMBF), participating German states and the German Cancer Research Center (DKFZ) and was established as one of six German Health Research Centres (DZGs). (http://www.dktk.org)

Information about Technische Universität Dresden (TUD)

The Technische Universität Dresden (TUD) is one of the eleven Universities of Excellence in Germany. This title acknowledges not only the outstanding research performance, but also the successful establishment of interdisciplinary research alliances. One of the five scientific profiles is represented in the cluster "Health Sciences, Bio-Medicine and Bio-Engineering", which combines basic and translational research. The scientific field of systems biology constitutes a new research area that is relating experimental and theoretical research to each other. Through a specific strategic prioritization at the Medical Faculty of the TU Dresden productive synergies among clinicians and researchers could be significantly expanded and led to the foundation of personalized medicine in Dresden. (https://tu-dresden.de/)

Contact Public Relations Dresden

Konrad Kästner
Tel: 0351 458 15486
Email: konrad.kaestner@tu-dresden.de

Scientific Contact Person:
Prof. Dr. Frank Buchholz
Medizinische Fakultät, Technische Universität Dresden
01062 Dresden
Tel.: 0351 463-40277 / 0351 463-40288
Email: frank.buchholz@tu-dresden.de

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