HIPS-Talk: “Design of non-viral gene delivery systems for gene therapy and vaccination: input from studies of nuceic acids intracellular delivery“
Recent clinical trials of gene therapy unambiguously demonstrate the potentiality of this innovative therapy to cure diseases related to genetic disorders. Even though viral delivery systems remain the best vehicles to introduce genes into cells; there are some adverse events that raise serious safety concerns. Therefore, clinical developments still require the use of alternative approaches of high safety, low immunogenicity and easy manufacture. Efforts have been carried out to design chemical gene delivery systems that incorporate viral-like features required for efficient cell transfection. Nucleic acids therapeutics are nanosized particles made of self-assembled nanometric complexes resulting from interactions between nucleic acids and chemical vectors. These nanosized particles are quite different to conventional drug delivery formulation. To bypass the different intracellular barriers, these vectors bear devices assembled on the same multifunctional vehicle but have to work independently and sequentially. Hence, it is crucial to know the fate of chemical vectors and nucleic acids complexes once inside the cell in order to improve their design.
I will present during this lecture, how by investigating intracellular delivery, we improved the design of both chemical vectors and nucleic acids. In combination with classical physico-chemical studies, confocal microscopy-based experiments including colocalization, FRAP/FRET/FLIM, videomicroscopy and single particle tracking were widely exploited to either validate the improvement obtained or pinpoint some limitations.
Knowledge and understanding the intracellular processing and routing of nucleic acids/chemical vectors complexes are crucial if we intend to build artificial viruses for efficient gene therapy and vaccination.
Gebäude und Raum
Blg C4 3, Kleiner Hörsaal der Anorganischen Chemie
Dr. Chantal Pichon
Center for Molecular Biophysics, CNRS UPR4301
affiliated to University of Orléans