Dipl. Pharm. Julia Giselbrecht
Analysis of cationic lipid formulations for the transfer of polynucleotides for the non-viral gene therapy
The approval of the first genetic therapeutic agents in Europe Glybera® (2013) and Strimvelis® (2016) has shown their high potential for the gene therapy as a new causal therapy.
Gene therapy is defined as the correction of defective genes or their regulatory elements by the insertion of nucleic acids into a living organism with the aim to prevent or to cure diseases.
Vectors are necessary for a successful gene transfer, which transport the nucleic acids into the target cell. These vehicles can be classified into viral and non-viral vectors. Retroviruses, adenoviruses, adeno-associated viruses and lentiviruses are used as viral vectors. The utilization of viral vectors for the gene transfer can be defined as transduction. Another possibility is the use of non-viral vectors like cationic lipids or cationic polymers for the complexation of anionic DNA-molecules. The transfer of therapeutical genes by the help of non-viral vectors is called Transfection and with the help of lipids as gene shuttles on speaks of lipofection.
Especially cationic lipids have a low immunogenicity, can easily be produced and are able to transport large amounts of DNA into the target cell. Therefore our research activities are focused on these cationic lipids and we produced them on ourselves in our department. To transport therapeutic genes into a cell it is necessary to create liposomes by the help of cationic lipids. These cationic lipids are combined with so called helper-lipids in order to increase the stability, and the transfection efficiency. These liposome mixtures are called lipoplexes and are later used for the complexation of DNA.
The characterization of those lipoplexes with regard to efficiency, stability and biocompatibility is the main focus of our research activities. Thereby a comprehensive characterization of the lipoplexes within the physiological milieu is the objective in order to create a stable system with high transfection efficiency and low toxicity. Therefore we are using a variety of methods such as for example the dynamic light scattering, agarose gel electrophoresis, zeta potential measurements, SDS-Page, TEM and in-vitro studies on cell culture models.
Publications
S. R. Pinnapireddy, J. Giselbrecht, B. Strehlow, C. Janich, C. Husteden, A. Meister,H. Loppnow, D. Sedding, F. Erdmann, G. Hause, G. Brezesinski, T. Groth, A. Langner, U. Bakowsky, Christian Wölk. A triple chain polycationic peptide-mimicking amphiphile – efficient DNA-transfer without co-lipids. Biomater. Sci., 2020,8, 232-249 [more]
J. Giselbrecht, S. Wiedemann, S. R. Pinnapireddy, N. Goergen, H. Loppnow, D. Sedding, F. Erdmann, U. Bakowsky, G. Hause, M. Lúcio, A. Langner, C. Wölk. Nucleic acid carrier composed of a branched fatty acid lysine conjugate—Interaction studies with blood components. Coll. Surf. B. 2019, 184, 110547, [more]
M. Schmid, C. Wölk, J. Giselbrecht, K.L.A. Chan, und R.D. Harvey: A combined FTIR and DSC study on the bilayer-stabilising effect of electrostatic interactions in ion paired lipids. Coll. Surf. B. 2018, 169, 298-394. [more]
S. Tassler, D. Pawlowska, C. Janich, J. Giselbrecht, S. Drescher, A. Langner, C. Wölk und G. Brezesinki: Lysine-based amino-functionalized lipids for gene transfection: the influence of chain composition on 3D phase behaviour and transfection performance. PCCP 2018, 20, 17393-17405. [more]
J. Giselbrecht, C. Janich, S.R. Pinnapireddy, G. Hause, U. Bakowsky, C. Wölk, und A. Langner: Overcoming the polycation dilemma - Explorative studies to characterise the efficiency and biocompatibility of newly designed lipofection reagents. Int. J of Pharm. 2018, [more]
conference contributions
J. Giselbrecht, J. Bussmann, A. Langner, C. Wölk
In-vivo studies with the zebrafish embryo model of different nucleic acid formulations with the cationic lipid OH4
Symposium "CRS German Chapter" 2020
J. Giselbrecht, J. Bussmann, A. Langner, C. Wölk
Presentation of a biocompatible and efficient nucleic acid delivery system - In-vivo and in-vitro studies of new cationic lipoplexes
Leipzig Research Festival of Lifescience 2020
J. Giselbrecht, J. Bussmann, A. Langner, C. Wölk
From in-vitro assays to in-vivo application studies- new cationic lipoplexes in comparison
Annual Meeting of the German Pharmaceutical Society 2019 (DPhG Heidelberg)
J. Giselbrecht, J. Bussmann, A. Langner, C. Wölk
Comparative in-vitro and in-vivo studies of cationic lipoplexes
International Congress Nanotechnology in Medicine & Biology (BioNanoMed) 2019
J. Giselbrecht, J. Bussmann, A. Langner, C. Wölk
In-vitro and in-vivo studies of cationic lipoplexes for gene therapy – from hemolysis assay to zebrafish experiments
Symposium "CRS German Chapter" 2019
J. Giselbrecht, S.R. Pinnapireddy, U. Bakowsky, A. Langner, C. Wölk
Physiological barriers after systemic application of lipoplexes - Study of the transfection limiting obstacles after systemic application
International Conference and Workshop on Biological Barriers 2018
J. Giselbrecht, S.R. Pinnapireddy, U. Bakowsky, A. Langner, C. Wölk
Analyses of the physiological barriers after systemic application of lipoplexes of T14diLys
Symposium "CRS German Chapter" 2018
J. Giselbrecht, S.R. Pinnapireddy, U. Bakowsky, A. Langner, C. Wölk
Analysis of the complexation behaviour and stability of lipoplexes in physiological media
Annual Meeting of the German Pharmaceutical Society - DPhG 2017
J. Giselbrecht, S.R. Pinnapireddy, U. Bakowsky, A. Langner, C. Wölk
Comparativ analyses of lipoplexes regarding their complexation behaviour and stability under physiological conditions
Symposium "Phospholipids in Pharmaceutical Research" 2017
S. Müller, A. Ewe, J. Giselbrecht, C. Wölk, A. Aigner, M.C. Hacker, M. Schulz-Siegmund
Liposome and polymer based siRNA transfection in hASC and SaOS-2 cells
Biotechnology Symposium - University Leipzig 2017
J. Giselbrecht, S.R. Pinnapireddy, U. Bakowsky, A. Langner, C. Wölk
Peptide-Mimicking Lipids in Gene Therapy – Investigation of Stability in Serum
Symposium "CRS German Chapter" 2017