Antonia Geyer of the University of Vienna was one of two recipients of the ESGCT Young Investigator Award at the 2016 National Meeting of the German Society for Gene Therapy.
Below, she sends us an overview of her research.
Outline of my Research:
In order to investigate the efficacy of gene therapy in preclinical settings, my research focuses on establishing of transgenic reporter models and the evaluation of pharmacokinetics as well as efficiency of non-viral gene delivery systems using multimodal imaging techniques. These imaging techniques include the spatio-temporal tracking of fluorescently labelled nucleic acids and evaluation of the efficacy using bioluminescence expressing cells or luciferase based vectors. Combining these molecular approaches with micro Computed Tomography (µCT) and Magnetic Resonance Imaging (MRI), information about the (physiological) morphology, e.g. position and size of organs but also the tumour load can be gained and co-registration with anatomical structures as well as quantification of the signal in the living organism can be achieved. Due to the minimal-invasive nature of this method, the effects of administered formulations can be monitored in real-time and also at different time points over a longer time period in one individual. In addition, the utilization of transgenic mouse models expressing luciferase selectively in organs or tissues of interest allows to study the efficacy of targeted gene transfer systems. The obtained results are verified afterwards using morphological histology combined with immunohistochemistry or standard molecular biology techniques, e.g. qPCR and luciferase assays.
What I won the award for: The intention of my poster was supposed to show the minimal-invasive, real-time distribution and quantification of NIRdye-labelled nanoparticles in comparison to stabilized naked siRNA after microspraying the formlulation directly into the lungs. Despite of biodistribution into the kidneys within 24 hours, fluorescence could still be detected in the lungs at this time point. The analysis of the urine showed, that in both formulated and unformulated groups intact siRNA could be detected indicating at least impaired degradation.
What it means: Preclinical studies are a critical step in the development of new drug formulations. On the one hand, it is the connection and last step prior to the translation into human application and on the other hand, animal numbers and improvement of applied techniques should be optimized in respect to Refinement and Reduction ("3R-replace, reduce, refine"). Minimally invasive, preclinical optical imaging gives us valuable insights into pharmacokinetics in real-time, provides us a peephole into the complexity of the organism and reduces the number of animals needed to obtain the data.
If you would like to find out more about the ESGCT Award Scheme, you can do so here, including listening to some of our past winners speak about their experiences!