Daniela Cesana holds a PhD in Cellular and Molecular Biology (2010) from Vita-Salute San Raffaele. After her MS in Medical Biotechnology from the University of Milan, she moved to San Raffaele Telethon Institute for Gene Therapy where she focused her attention on the safety of gene therapy approaches with integrative vectors. Here, she established a preclinical mouse model able to provide an accurate evaluation of the oncogenic risks associated with the use of integrating vectors and prompt the use of lentiviral vectors for clinical applications.  During her PhD, she continued to dissect the mechanism of crosstalk between regulatory elements contained within the expression cassette of an integrated vector and the surrounding host cellular genome. In 2016, she received her first young investigator grant from the Italian Ministry of Health, which allowed her to identify that, as other retroviruses, HIV-1 can interfere with the transcription of the host cellular genes surrounding the integration sites to favor its persistence in the host. More recently, she has deepened her knowledge in genomics and bioinformatics by designing new technologies and computational tools that allow the retrieval of integration sites from cell-free DNA and the identification and characterization of Adeno Associated Vector (AAV) integration sites in different preclinical models of gene addition and gene editing. Overall, she has a multidisciplinary background in molecular and cell biology and genomics. Nowadays, she is Program Leader at San Raffaele Telethon Institute for Gene Therapy and Project Leader at the Safety and Insertional Mutagenesis unit.

Research activity

The scope of the program is the development and validation of a cfDNA-based pipeline able to capture the spatio-temporal complexity of biological responses occurring in patients who underwent gene therapy for the treatment of inherited and acquired genetic diseases. cfDNA is a mixture of fragments released from healthy and diseased cells in different tissues throughout the human body into circulation. Tissue of origin studies allows tracing cfDNA molecules back to the tissue and cell types they originated from and use changing tissue proportions to reveal altered tissue homeostasis and diseased states or therapy-related toxicity. By using state-of-the-art molecular approaches, the program aims at characterizing those cfDNA signatures to reveal what is occurring in diseased patients at the whole organismal level pre and after-therapy to provide insights into the different phases of disease progression, inform the effectiveness of the therapy, and possibly guide the selection of patients who would benefit from the treatment.