Rabies virus (RV) can infect neurons via retrograde transport, from postsynaptic to presynaptic cells. RV is also an attractive candidate for gene delivery, as it can provide fast and high expression of transgenes that can be potentially used in gene therapy of degenerative diseases. Genetic modifications of the envelope glycoprotein (G) can impact the selectivity of RV infections, and such modification has been successfully applied to manipulate RV in the TVA/EnvA system. Pseudotyping of G-deleted RV (RVt. G) with chimeric protein consisting of the ectodomain of EnvA protein and the cytoplasmic domain of G protein enables to restrict initial infection with RV to cells expressing non. mammalian TVA receptor, delivered by Adeno Associated Virus (AAV) helper viral vector (F. Osakada el a/., 2013). Expression of transgenes in AAV plasmids is driven by an upstream promoter that can be constitutive or cell-type specific, therefore specificity of infection can be uniquely controlled on that level (C. Domenger et al., 2019). The main goal of our projects is to use AAV vectors and RV as gene therapy tools, that specifically infect cells within the retina, to treat retinal degenerative diseases. We have managed to isolate promoters to drive the expression of transgenes in specific types of cells within the retina. Further, we demonstrated that pseudotyping of Viral Like Particles (VLPs) with chimeric G proteins enables them to infect desired cells, and this approachemical is going to be used for the pseudotyping of RV Indeed, our results indicate that RV is a potential tool for effective gene therapy, as we successfully, simultaneously transduced retinal cells with up to four different transgenes. Further analysis will reveal the therapeutic effect of performed gene deliveries
About the speaker
Dr Jagoda Płaczkiewicz is a postdoctoral researcher in the Ophthalmic Biology Group at ICTER, working in molecular biology. Her experimental work focuses on engineering new variants of viruses that may be used as tools for gene therapy
