Our Research Focus
Where the Unknown becomes Reality
The Gene Therapy Unit focusses on the most commonly used gene therapy vectors: adenoviral, adeno-associated viral (AAV) and lentiviral vectors. Our goal in vector development programs is to develop safer, regulated and more efficient viral vectors. An understanding of disease at the molecular biology level is key to the way KCT operates and our developed viral vectors are tested in vitro and in vivo models of disease to obtain a clear proof of principle at the molecular biology level.
Translational stage work comprises extensive manufacturing process development, analytical development, mechanistic proof of principle in the target disease and preclinical animal studies. Our early stage gene therapy manufacturing process development and process scale-up encompasses;
- Adenoviral, AAV and lentiviral vectors
- Adherent process platforms (iCELLis technology)
- Suspension process platform (Cultibag and stirred tank bioreactor)
- Clarification, depth filtration, polish filtration
- Chromatographic AEX, affinity purification
- Tangential flow filtration
- Final formulation.
The research of the Cell Therapy Unit focuses on innovative cell therapies and ex vivo cell editing. Researchers are working on developing therapies to patients suffering from cancers, cardiovascular and autoimmune diseases. Early research on cell characterization includes traditional and ‘omics’ methodologies to support product development and the critical quality attributes definition relevant to the mode of action and safety. Therapeutic potential and modes of action are examined using in vitro methods and relevant animal models. We take pride in our process development on finding the best solution for automated, closed processes that can ensure robust and reproducible product manufacturing.
Examples of KCT’s Cell Therapy Unit capabilities include;
- Automated and manual cell enrichment
- Bioreactor testing for adherent and suspension cultures
- Downstream wash and formulation solutions
- Single-cell sorting in a BSL2 environment.
Accurate and advanced analytics is an essential core capability in the ATMPs area. KCT‘s Analytical Core Unit provides ‘state of the art’ analytical capabilities to support daily routine research level analytics, to develop new assay approaches, to provide technical help and training to researchers and to track the development of analytical technologies.
Examples of our analytical capabilities for virus, cell and molecular biology applications include:
- Immunoassays: ELISAs, western blots
- BCA, picogreen, spectrophotometry
- Polymerase chain reactions: ddPCR, qPCR, PCR
- Flow cytometry analyses (+cell sorter)
- Fluorescence microscopy, transmission electron microscopy (TEM)
- Dynamic light scattering (DLS)
- Bioinformatics, large data analysis.
Kekarainen T and Lesch HP. Welcome to the Kuopio Center for Gene and Cell Therapy. Health Europa Quarterly Issue 6. Aug 2018.
Valkama AJ, Leinonen HM, Lipponen EM, Turkki V, Malinen J, Heikura T, Ylä-Herttuala S, Lesch HP.
Optimization of lentiviral vector production for scale-up in fixed-bed bioreactor
Gene Ther. 2018 Jan;25(1):39-46.
Belt H, Koponen JK, Kekarainen T, Puttonen KA, Mäkinen PI, Niskanen H, Oja J, Wirth G, Koistinaho J, Kaikkonen MU, Ylä-Herttuala S.
Temporal Dynamics of Gene Expression During Endothelial Cell Differentiation From Human iPS Cells: A
Comparison Study of Signalling Factors and Small Molecules.
Front Cardiovasc Med. 2018 Mar 14;5:16. doi: 10.3389/fcvm.2018.00016.
Turkki V, Lesch HP, Ryner M, Nilsson J.
Viral vector particle integrity and purity analysis in early process development.
BioProcess Int. 2017; 15:34-37.