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Laboratory of Macromolecular Cancer Therapeutics (MMCT)

Research Team

 

researcherfunctionfield of research
Manfred Ogrisprinciple investigatormolecular cancer therapeutics
Sebastian Gehrigpostdoctoral research fellowmolecular imaging, comparative medicine
Haider Samipostdoctoral research fellowbionanomaterials development
Magdalena BillerhartPhD studentcancer immuno-gene therapy
Antonia GeyerPhD studentmolecular imaging, transgenic models
Julia MaierPhD studentmolecular biology of cancer
Alexander TaschauerPhD studentnucleic acid carrier development

Research mission

Besides cardiovascular disease, malignant diseases are the major cause of death in the western world. First line treatment, i.e. surgical resection of the primary lesion, followed by radio- and chemotherapy is often successful in the beginning, but with the onset of relapsing and metastasizing disease the onset of resistance towards chemotherapy and radiation is the major cause for the fatality of the disease. Hence, novel treatment options are necessary, which alone or in combination with current treatment options will help to control or even eradicate the malignancy. Nucleic acid based drugs offer a unique platform for the development of cancer specific treatment options.

At the Laboratory of Macromolecular Cancer Therapeutics (MMCT) we develop novel drug formulations for the targeted delivery of therapeutically active compound into cancerous tissues. There is an emphasis on delivery vectors for nucleic acids, including fully synthetic systems, recombinant viruses or combinations thereof. Multifunctional nanocarriers for nucleic acids are synthesized and characterized by pysico-chemical methods. The interaction of particles with cancer cells is studied by fluorescence microscopy techniques and flow cytometry.  Several syngeneic and xenograft tumor models are established, where nanoparticle pharmacokinetics and pharmacodynamics are monitored. Molecular imaging techniques also enable us studying therapy response in the living organism with the help of bioluminescence measurements and near infrared spectroscopy imaging.

Our research projects include the development of delivery systems for nucleic acids (see project Targeted gene delivery); for achieving strong and sustained transgene expression, novel plasmid vectors are designed (project plasmid vectors).

Hybrid gene delivery systems are developed, where adenoviral vectors are coated with molecular conjugates to achieve re-targeting of the vectors (project adenovirus coating). To achieve tumor restricted transgene expression of therapeutically active proteins, either specific promoters are used (project plasmid vectors), or the aberrant expression profile of micro RNA in cancer (see project miRNA restricted transgene expression).

In addition to DNA vectors, we also deliver small interfering RNA molecules (siRNA) for the selective knockdown of molecular targets in cancer cells (project wnt pathway targets in colon cancer). Systemic delivery is necessary in case of already metastastasized disease. Biodistribution and functionality of gene vectors is studied with biooptical methods, including bioluminescence imaging (BLI) and near infrared imaging (NIR) (project Bioimaging).

Therapeutic success in cancer treatment also relies on suitable treatment concepts, which synergize with standard treatments like radiation or chemotherapy achieving potent bystander effects within the tumor tissue. In the project TNFα enhanced cancer gene therapy, the expression of the potent cytokine TNFα within tumor tissue in combination with liposomal chemotherapeutics allows selective antitumor treatment.

Division of Clinical Pharmacy and Diagnostics
University of Vienna
Althanstraße 14
A-1090 Wien, Austria

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