Product name
Bacterial Vector for Medical Use gradually inducible in vivo at Will by Exertion of external InfluenceSummary
Attenuated invasive bacteria serve as bacterial vectors for vaccines eliciting an immune response against a peptide foreign to the bacterial vectorOrganization name
Ascenion GmbHProfile
Attenuated bacteria are used for genetic vaccination and gene therapeutic purposes as carrier vehicles to introduce eukaryotic expression plasmids into mammalian cells. For all these applications, it is desirable to control the level of expression of the respective peptide(s) and/ or copy number of nucleic acids.
Up to now, most attempts to do so rely on constitutive promoter sequences. Recently, also in vivo inducible promoters were used. A major disadvantage of these promoters is that they automatically respond to specific phases of the infectious cycle of the bacterium, and therefore cannot be regulated by exerting an external influence.
The Technology
The present technology provides bacterial vectors for medical use on the basis of non-invasive (e.g. commensal) or invasive bacteria. The activity of the tightly regulated expression cassette contained in these vectors can be regulated "from the outside" at will by administration of respective inductor doses. The expression cassette comprises the transgene operably linked to a saccharide inducible promoter (most preferably arabinose inducible promoter element PBAD).
Considerable advantages of this inducible promoter are its tight regulation in absence of inductor and its dose-dependant response to gradually increasing concentrations of inductor substance (e.g. arabinose) in form of gradually increasing activity. Furthermore, required inductors are non-toxic to the target cell and organism and can be administered via several routes. Proof-of-principle is established in vivo.
Commercial Opportunity
The inventive bacterial vectors have distinct advantages for numerous medical applications covering the fields of tumour therapy, (genetic) vaccination, immune and gene therapy, as well as diagnostics, e.g. the marking of tumour cells. The technology may also be explored in the functional food sector. Key advantages are
- Independency of promoter regulation from bacteria cell cycle
- Option to gradually induce the tightly regulating promoter element allowing for individual (patient-specific) regulation of the medical activity of the respective transgene.
- Respective inductor substances are saccharides, preferably arabinose. They are non-toxic to the target cell/organism, well studied and can be administered orally, intravenously, intraperitonally, intramuscularly or parenterally depending on the medical needs.
European and PCT application pending.
Contact
Tina Damm
damm(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.
Description File
02-00126_TO_in_vivo_modulation.pdf
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