StressHSC - Finalizzata GR-2016-02363681 (DSB.AD008.634)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Institute of biomedical technologies (ITB)

Project manager

IVAN MERELLI
Phone number: 02 26422602
Email: ivan.merelli@itb.cnr.it

Abstract

Hematopoietic stem cell (HSC) Gene therapy (GT) applications based on retroviral vectors are now effective treatments for several inherited monogenic diseases. Integration site (IS) studies are an invaluable tool to monitor the corrected HSC in vivo. However, IS data cannot reveal any information on the proliferative properties of the HSC over time, important parameters to evaluate the safety of GT. The hematopoietic system reconstitution after transplant induces HSC in proliferation stress, a potent driver of functional decline. Since the accumulation of genomic somatic mutations can be a sensor of the proliferative cell stress, we will characterize the proliferation stress of HSC and their progeny in the different phases of the hematopoietic reconstitution by the accumulation of mutations in the vector/host genome junction sequences. This approach will improve the safety and efficacy of HSC GT procedures towards the development of effective and disease specific GT protocols.

Start date of activity

03/09/2018

Keywords

Gene Therapy, Hematopoietic stem cell, proliferation stress

Last update: 03/05/2024