Project

Stress HPC

Improving the safety and long-term efficacy of hematopoietic stem cell-based Gene Therapy and optimization of the treatment protocol through in vivo characterization of the stem cell proliferation stress during the hematopoietic reconstitution.
Application Areas
Research Areas
Research Lines
Staff
WEBSITE

ITB Principal Investigator

Name

Improving the safety and long-term efficacy of hematopoietic stem cell-based Gene Therapy and optimization of the treatment protocol through in vivo characterization of the stem cell proliferation stress during the hematopoietic reconstitution.

Acronym

Stress HPC

Location

Segrate

Start Date

2018

End Date

2022

Funder

Ministero della Salute

Partners

San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy

Gene therapy (GT) applications based on retroviral vectors in hematopoietic stem cells (HSCs) are now effective treatments for several inherited monogenic diseases. The study of integration sites (IS) is a valuable tool for monitoring corrected HSCs in vivo. However, IS data do not provide information on the proliferative properties of HSCs over time, which are important parameters for assessing GT safety. Haematopoietic system reconstitution after transplantation induces proliferative stress in HSCs, a potent driver of functional decline. Since the accumulation of genomic somatic mutations can be an indicator of proliferative cellular stress, we will characterise the proliferative stress of HSCs and their progeny at different stages of haematopoietic reconstitution through the accumulation of mutations in vector/host genome junction sequences. This approach will improve the safety and efficacy of HSC GT procedures towards the development of disease-specific protocols.