Micco Lab

San Raffaele Hospital

Nord-Ovest (ITC) · Italy

ERC-funded
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Research focus

ERC Consolidator Grant · 2020

Dissecting and targeting senescence programs to advance Hematopoietic Stem Cell-based gene therapies

The success of Hematopoietic Stem and Progenitor Cell (HSPC) gene therapies critically depends on the capacity to genetically engineer HSPCs without compromising their functional properties. Emerging evidence, including our own, indicates that HSPC exposure to currently available gene transfer and gene editing technologies –which require prolonged ex-vivo culture, high viral vector doses and nuclease-induced DNA double strand breaks– unexpectedly converge on the DNA damage response (DDR), a signaling cascade leading to cell cycle arrest. Protracted DDR impairs the hematopoietic reconstitution of gene-modified cells upon transplantation; instead, its transient inhibition significantly…

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