Modeling and understanding of genetically modified systems as a whole

This project aims to characterize vector integration sites present in blood plasma DNA (circulating DNA) or other body fluids in patients undergoing gene therapy as a possible reading of the clonal composition of genetically modified cells residing throughout the body and not exclusively on peripheral blood. As part of this project, we have developed a technique (Liquid Biopsy Integration Site sequencing, LiBIS-seq) capable of recovering integrations of vectors from circulating DNA.
This technology allows for the early detection of vector-induced tumors located outside the bloodstream and/or before the obvious appearance of circulating malignant cells. Another aim of this project is to investigate proliferative stress after transplantation of genetically modified hematopoietic stem cells in gene therapy patients by measuring the rate of somatic mutations in the genomic sequences flanking the integration sites in different types of hematopoietic cells and in the time.