Research Abstract
The Genovese lab is a translational gene therapy research group that exploit a variety of cutting-edge gene editing technologies (CRISPR/Cas, TALEN, ZFN, base editors, epigenetic transcriptional regulators) to develop new therapeutic strategies for inherited and oncologic diseases. We couple advanced molecular and cell biology approaches, such as viral vectors design, chimeric antigen receptors (CAR), next generation sequencing and ex vivo manipulation of stem cells and primary lymphocytes, with suitable preclinical models of disease to test novel therapeutics based on precision medicine both in vitro and in vivo. We originally developed the T cell receptor gene editing strategy to improve safety and efficacy of cancer adoptive immunotherapies (Provasi* Genovese* et al., Nat Med. 2012). This innovative approach is now widely used in the immunotherapy field for generating allo-compatible T cells or to express CAR genes under the control of endogenous TCR promoter. We also developed the first protocol that allow targeted gene editing in human hematopoietic stem/progenitor cells capable of long-term multilineage repopulation (Genovese at al., Nature 2014) and we are currently exploiting recent advancements of this technology for generating a “stealth” hematopoiesis that is resistant to aggressive and prolonged CAR T cell therapies for the treatment of acute myeloid leukemia. Finally, we are using advanced genetic engineering tools for obtaining a new class of in vivo vaccine for activating immune responses against solid tumors.
