Product name
Modified Self-Inactivating Retroviral Vectors with Enhanced Titer, Expression Rate, and BiosafetySummary
modified sequences suitable for lentiviral and gammaretroviral vectors allow high infectious titer preparations, high activity of the transgene, and reduced risk of transcriptional readtroughOrganization name
Ascenion GmbHProfile
Retroviruses are widely used as gene delivery tools. Because the retroviral genome inserts into the host cell genome following infection, it can be utilized as a permanent gene delivery vehicle. To produce retroviral vectors in so called packaging cells, co-transfection of different plasmids is necessary. To yield high titers of viral preparations, the plasmid encoding the vector RNA needs to be equipped with an efficient 5´ promoter. While wild-type enhancer-promoter elements in the U3 region lead to high transcription rates, they carry the risk of upregulating neighbouring genes by insertional mutagenesis.
The alternative use of internal SIN elements eliminates this risk, but infectious titers of viral preparations are reduced 10-fold, representing a major limitation for their clinical use. Furthermore, the deletion of U3-sequences as present in state-of-the-art SIN vectors impedes retroviral transcriptional termination and polyadenylation. This may contribute to low titers and also reduce transgene expression in target cells. Insufficient termination of transcription also increases the risk of transcriptional readthrough and splicing of mRNA into downstream located cellular genes.
Technology
The technology relates to modified sequences suitable for lentiviral and gammaretroviral vectors that allow high infectious titer preparations, high activity of the transgene, and reduced risk of transcriptional readtrough. Application of these modifications does not only improve vector efficiency and biosafety, but reduces cost of production as well.
Developmental Status
Improvement of titer, transgene expression and transcriptional readtrough prevention has been verified in cell culture.
European, Japanese and US applications have been filed.
Contact
Dr. Ralf Cordes
cordes(at)ascenion.de
About Ascenion
Ascenion is the exclusive partner of 12 life-science institutes in the Helmholtz and Leibniz Associations and of one Medical School, and coordinates technology transfer for the German National Genome Research Network. They currently market around 600 technologies, together with a varied range of research materials, e.g. antibodies, animal models and vectors.
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