Improving the safety of LV integration and molecular monitoring technologies

In this research area we use mouse models and new technologies to unravel the basic mechanisms governing genotoxicity and compare the impact of integrating lentiviral vectors containing genetic elements to improve their safety. We aim to capitalize on the knowledge gained to design and validate novel lentiviral vectors with an improved safety profile to be adopted in future ex vivo and in vivo gene therapy applications.
With the use of ultra-sensitive mouse models we have shown that lentiviral vectors containing genetic sequences called isolators recognized by the CTCF factor and sequences recognized by microRNAs have a significantly higher biosafety profile than unmodified vectors.
Furthermore, we have developed genomic technologies to evaluate the impact of vector integration on the chromatin structure at the three-dimensional level (LV-4C and HiC); Thanks to these techniques we discovered that lentiviral vectors armed with insulator sequences establish long-range unidirectional genomic interactions. The integrated vector therefore tends to form genomic areas, thus reducing the likelihood of gene activation.