Discovery of the possibility to transfer nucleic acids (genes, siRNA, antisense oligonucleotides, mARN) into mammal cells has been a wonderful opportunity to create new tools in fundamental research but it also allowed development of new therapeutic approaches in human medicine. For example, the transfer of siARN is very promising whenever degrading a specific mARN could lead to a therapeutic effect as in cancers, viral infections or genetic and neurodegenerative diseases.
However, such therapeutic potential requires the development of vectors able to efficiently transfer nucleic acids to and into the target cells. As nucleic acids are anionic polymers, they cannot cross biological barriers like cell membranes. Currently available synthetic formulations which can vectorize DNA or siRNAs in vitro exhibit rather poor results in vivo. It is one of the great current challenges to develop and synthesize efficient and safe ways to transfer nucleic acids in vivo.
Part of our team’s work consists in creating new vectors for gene transfer. They are mostly lipids, polymers and cationic peptides which can condense and transport nucleic acids but also are tailored so their intrinsic properties improve efficiency of the global transfection process by responding to intracellular stimuli (pH, redox potential, enzymatic activity).
Those vectors are then given fusogenic and/or endosomolytic activity, tensioactive power, targeting properties... Particular attention is given to their biodegradability. As a matter of fact, cationic vectors’ toxicity arises for most part from their accumulation in cells and tissues. Biodegradability must then be taken into account right from the beginning when designing the molecular structure of a new vector. Another transfection strategy developed in our team consists in modifying the nucleic acids with spermine groups to mask/neutralize charges of the anionic polymer which leads to "self-transfecting" nucleic acids.
The team V-SAT is also developing different systems to achieve vectorization of proteins. Our goal is to develop formulations to improve pharmacological properties of proteins, and more especially of antibodies. In parallel, we work to set up 3D cell cultures (spheroid). That type of cell culture better mimics the heterogeneity of a micro-tumor which makes it a more efficient tool than "classical" culture to evaluate systems of vectorization.
With our experience in organic synthesis, we also work in the design of probes : fluorescent probes (coumarins, Cy5s...), time-resolved fluorescent probes (lanthanide complexes), near-infrared fluorescent probes for in vivo studies (ICG, C-dots...). In different research programs inside our team or in collaboration, those probes are coupled to various bioactive compounds which allows a better understanding of some biological processes.