Retrovirus-based Vectors for Transient and Permanent Cell Modification

Group Members: Girmay Asgedom, Elke Barczak, Emanuele Coci, Melanie Galla, Franziska Geis, Dirk Hoffmann, Johannes Kühle, Tobias Mätzig, Thomas Neumann, Juliane Schott, Julia Sürth, Diana Szepe, Verena Thies, Ina von Wechgeln, Jessica Wenzl, Daniela Zychlinski

The ongoing improvement of gene transfer vectors for hematopoietic and other cell types has a strong impact for the application in clinical trials. Our team focuses on the design and evaluation of novel safety-modified retroviral vectors, derived from gamma-, lenti- and alpharetroviruses. Alpharetroviral vectors represent an interesting addition to the vectorologist’s toolbox. Originally described not to replicate in mammalian cells, we have managed to design and produce alpharetroviral SIN vectors, which maintain the favorable and neutral alpharetroviral integration pattern.

Key interests of our lab include the understanding of vector-host interactions regulating transcriptional and post-transcriptional events of transgene expression, and the analysis of post-entry mechanisms of retroviral particle processing. Based on this work the lab generates improved vectors for reversible cell modification or long-lasting transgene expression. Following detailed analyses in preclinical model systems, a number of national and international collaborators have started clinical trials with vectors developed by our team, e.g. the recent SCID-X1 trial in Boston, Paris and London. Further clinical trials may be initiated in the future.

Another example for the applicability of our vector toolbox is the efficient and flexible generation of induced pluripotent stem cells (iPSC), a pluripotent stem cell population that can be developed from somatic cells by retroviral overexpression of 4 transcription factors. Especially patient-specific iPSC can be exploited to model diseases and to test novel molecular medicine interventions, e.g. gene therapy.

Selected own references: Suerth et al., Mol Ther 2012; Schott et el., Curr. Gene Ther. 2011; Maetzig et al., Blood 2011; Voelkel et al., PNAS 2010 

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