Basic Research

Research at SR-Tiget spans from basic research to pre-clinical studies to early phase clinical trials according to the following major aims:

• identifying the genetic bases and the pathophysiological processes underlying several types of inherited diseases, including primary immunodeficiencies and autoimmune/autoinflammatory diseases, hematologic diseases, inherited leukodystrophies and other lysosomal storage and neurodegenerative diseases;
• developing novel ex vivo or in vivo gene and cell therapy strategies for such diseases and validating them in ad hoc designed experimental models;
• ameliorating the performance and safety of gene transfer employed for these therapies, i.e. by stringently targeting transduction or expression of lentiviral vectors to the desired cell types and reducing their impact on endogenous transcription at genomic insertion sites;
• characterizing the biological properties of hematopoietic and neural stem and progenitor cells and of mesenchymal stromal cells targeted by these therapies and improving the procedures for their ex vivo isolation, genetic modification and transplantation;
• developing novel technological platforms, including targeted genome and epigenome editing using artificial enzymes with DNA sequence-specific activity (such as ZFN, TALEN and CRISPR-Cas9 nucleases) and scaffolds for ex vivo organoid culture (e.g. for hematopoietic stem cell niche reconstitution);
• investigating the cell types that mediate innate and adaptive immunity, with the aim to develop strategies to induce immunological tolerance to gene and cell products, in order to improve the efficacy and stability of such therapies;
• exploiting the platforms and strategies developed through the abovementioned investigations to design new gene and cell therapies for some common diseases, i.e. to induce tolerance in diabetes and other autoimmune diseases or, conversely, enhance adaptive immunity to cancer associated antigens.