Assistant Professor in Pediatrics, Harvard Medical School Faculty, Division of Hematology/Oncology, Boston Children's Hospital Faculty, Department of Pediatric Oncology, Dana-Farber Cancer Institute Associate Faculty, Harvard Stem Cell Institute
Dr. Pietro Genovese, Ph.D., is a Principal Investigator at the Gene Therapy Program of Dana-Farber/Boston Children’s Cancer and Blood Disorder Center and an Assistant Professor of Pediatrics at Harvard Medical School. In the last 20 years, he has dedicated his efforts to developing genome editing tools that improve the safety and efficacy of adoptive immunotherapy or promote safer applications of human stem cell gene therapy.
Working with the group of Luigi Naldini at the San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), he contributed to pioneering this field since when ZFNs were first shown to enhance gene targeting and be useful for the genetic engineering of somatic cells for therapeutic purposes. In 2007, he contributed to a break-through work where they demonstrated for the first time the possibility of exploiting ZFN to direct the integration of exogenous DNA sequences into a predetermined genomic locus of several human cell types (Lombardo, Genovese, et al., Nat Biotech 2008). During his Ph.D. studies, he extended his knowledge and skills in this technology by developing the T cell receptor gene editing strategy to improve the 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 the endogenous TCR promoter. As a post-doctoral associate, he engaged in an ambitious study aimed at correcting inherited mutations and developed the first protocol that allows targeted transgene integration in human hematopoietic stem cells (HSC) capable of long-term multilineage repopulation (Genovese et al., Nature 2014). As Project Leader, he coordinated a work team of scientists towards the goal of performing pre-clinical development and proof of feasibility of these novel medical treatments for some candidate diseases, chosen as paradigmatic for testing their therapeutic potential. His team has established optimized protocols that reduce the toxicity of the editing procedure (Schiroli et al., Cell Stem Cells 2019; Ferrari et al., Nat. Biotech. 2020) and have devised universal editing strategies for correcting the genetic defects in several inherited hematopoietic disorders (Schiroli et al ., Sci Transl Med 2017; Vavassori et al., EMBO Mol. Med. 2021). His first project conducted as principal investigator focused on the HDR-mediated correction of HIGM1 is now in advanced phases of manufacturing development, and a first-of-this-kind trial is expected to be opened at SR-Tiget two years from now.
In 2019, he established his own independent laboratory at the Dana-Farber/Boston Children’s Cancer and Blood Disorder Center and was appointed assistant professor at Harvard Medical School. As a faculty member, his current efforts are aimed at moving these advanced genetic engineering strategies toward an effective therapeutic treatment for inherited and malignant diseases. Dr. Genovese has recently established a new genetic engineering concept - named “epitope editing” - to generate a “stealth” hematopoiesis resistant to immunoglobulin-based drugs/CAR-T cells (Casirati et al., Nature 2023). This approach will provide novel opportunities to advance precision immunotherapies for relapsed/refractory leukemias and allow safer, non-genotoxic conditioning approaches for non-malignant HSC transplants.
Dr. Genovese is the author of several high-profile publications, co-inventor of more than ten patents on gene editing technology, and recipient of several awards, including the New Investigator Awards from the ESGCT (2016) and the ASGCT (2024) Societies.