Exploiting ex vivo expansion and deep multiomics profiling to bring novel, efficient and safer hematopoietic stem cell gene therapies to clinical application

Informations projet

X-PAND

N° de convention de subvention: 101070950

DOI

10.3030/101070950

Date de signature de la CE 15 Juillet 2022

Date de début 1 Octobre 2022

Date de fin 31 Mars 2027

Financé au titre de

• The European Innovation Council (EIC)

Coût total

€ 3 797 562,50

Contribution de l’UE

€ 3 797 562,50

Coordonné par

OSPEDALE SAN RAFFAELE SRL
Italy

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Livrables

Websites, patent fillings, videos etc. (1)

Setup of Project website, project logo and social media channels

Development and operation of the projects website development of project logo and development of social media channels

Publications

Peer reviewed articles (11)

p38 MAPK fuels proliferation stress and DNA damage impairing the functionality of genetically engineered hematopoietic stem and progenitor cells

Auteurs: Raffaella Di Micco; Lucrezia della Volpe; Roberta Vacca; Federico Midena; Teresa Tavella; Matteo Maria Naldini; Matteo Barcella; Kety Giannetti; Samuele Ferrari; Stefano Beretta; Giacomo Farina; Laura Alessandrini; Antonella Santoro; Edoardo Carsana; Angelica Varesi; Diego Gilioli; Anastasia Conti; Ivan Merelli; Bernhard Gentner; Luigi Naldini
Publié dans: Cell Reports Medicine, Numéro 5, 2024, ISSN 2666-3791
Éditeur: Elsevier Inc.
DOI: 10.1016/J.XCRM.2024.101823

Protocol for optimizing culture conditions for ex vivo activation during CRISPR-Cas9 gene editing in human hematopoietic stem and progenitor cells

Auteurs: Lucrezia della Volpe, Roberta Vacca, Raffaella Di Micco
Publié dans: STAR Protocols, Numéro 6, 2025, ISSN 2666-1667
Éditeur: Elsevier BV
DOI: 10.1016/J.XPRO.2025.103722

Ex vivo expansion of hematopoietic stem and progenitor cells from human mobilized peripheral blood for gene therapy applications

Auteurs: Erika Zonari, Matteo Maria Naldini, Matteo Barcella, Monica Volpin, Francesca Vincenti, Giacomo Desantis, Leila Hadadi, Carolina Caserta, Ilaria Galasso, Beatrice Martini, Federico Midena, Giacomo Farina, Roberta Vacca, Francesca Tucci, Leonardo Ormoli, Ilaria Visigalli, Michela Vezzoli, Dejan Lazarevic, Ivan Merelli, Stephanie Z. Xie, John E. Dick, Raffaella Di Micco, Eugenio Montini, Bernhard Gentner
Publié dans: Molecular Therapy, Numéro 34, 2026, ISSN 1525-0016
Éditeur: Elsevier BV
DOI: 10.1016/J.YMTHE.2026.05.014

p38 MAPK inhibition safeguards genome integrity during gene editing of hematopoietic stem and progenitor cells

Auteurs: Roberta Vacca, Lucrezia della Volpe, Nicolò Gualandi, Kohei Shiroshita, Edoardo Carsana, Kety Giannetti, Chiara Gaddoni, Fabrizio Benedicenti, Barbara Gega, Sergio Arévalo, Parinaz Zarghamian, Stefano Beretta, Maria Carmina Castiello, Chiara Brombin, Daniele Canarutto, Ivan Merelli, Toni Cathomen, Eugenio Montini, Anna Villa, Luigi Naldini, Raffaella Di Micco
Publié dans: Molecular Therapy, 2026, ISSN 1525-0016
Éditeur: Elsevier BV
DOI: 10.1016/J.YMTHE.2026.09.024

Selection of human hematopoietic stem cells bearing the intended functional edit by transient AND-gate reporters

Auteurs: Daniele Canarutto, Martina Fiumara, Vigneshwaran Venkatesan, Chiara Gaddoni, Kohei Shiroshita, Angelica Varesi, Luisa Albano, Gabriele Pelosi, Alfredo Silva, Claudia Firrito, Giulia Schiroli, Deborah Cipria, Stefano Beretta, Angelo Amabile, Anna Villa, Erika Zonari, Bernhard Gentner, Angelo Lombardo, Pietro Genovese, Samuele Ferrari, Luigi Naldini
Publié dans: Nature Biotechnology, 2026, ISSN 1087-0156
Éditeur: Springer Science and Business Media LLC
DOI: 10.1038/S41587-026-03142-Z

Genotoxic effects of base and prime editing in human hematopoietic stem cells

Auteurs: Fiumara M, Ferrari S, Omer-Javed A, Beretta S, Albano L, Canarutto D, Varesi A, Gaddoni C, Brombin C, Cugnata F, Zonari E, Naldini MM, Barcella M, Gentner B, Merelli I, Naldini L.
Publié dans: Nature Biotechnology, 2023, ISSN 1546-1696
Éditeur: Nature Biotechnology
DOI: 10.1038/s41587-023-01915-4

CRISPR-Cas9n-mediated ELANE promoter editing for gene therapy of severe congenital neutropenia

Auteurs: Masoud Nasri, Malte U. Ritter, Perihan Mir, Benjamin Dannenmann, Masako M. Kaufmann, Patricia Arreba-Tutusaus, Yun Xu, Natalia Borbaran-Bravo, Maksim Klimiankou, Claudia Lengerke, Cornelia Zeidler, Toni Cathomen, Karl Welte, Julia Skokowa
Publié dans: Molecular Therapy, Numéro 32, 2025, ISSN 1525-0016
Éditeur: Elsevier BV
DOI: 10.1016/J.YMTHE.2024.03.037

Gene editing of NCF1 loci is associated with homologous recombination and chromosomal rearrangements

Auteurs: Raimondi, Federica; Siow, Kah Mun; Wrona, Dominik; Fuster-García, Carla; Pastukhov, Oleksandr; Schmitz, Michael; Bargsten, Katja; Kissling, Lucas; Swarts, Daan C; Andrieux, Geoffroy; Cathomen, Toni; Modlich, Ute; Jinek, Martin; Siler, Ulrich; Reichenbach, Janine
Publié dans: Communications Biology, 2024, ISSN 2399-3642
Éditeur: Nature Portfolio
DOI: 10.5167/UZH-263302

DNA-dependent protein kinase inhibitors PI-103 and samotolisib augment CRISPR/Cas9 knock-in efficiency in human T cells

Auteurs: Emina Džafo, Morteza Hafezi, Greta Maria Paola Giordano Attianese, Patrick Reichenbach, Stephane Grillet, Hélène Garcia, Elisabetta Cribioli, Christel Voize, Stephanie Tissot, Romain Vuillefroy de Silly, George Coukos, Kirsten Scholten, Melita Irving, Bernhard Gentner
Publié dans: Cytotherapy, 2025, ISSN 1465-3249
Éditeur: Elsevier BV
DOI: 10.1016/J.JCYT.2025.02.001

Nanoengineered 3D culture substrate enables superior persistence and polyclonal engraftment of genetically engineered hematopoietic stem cells

Auteurs: Federico Midena, Laura Alessandrini, Claudio Conci, Matteo Barcella, Francesco Gazzo, Emanuela Jacchetti, Edoardo Carsana, Fabrizio Benedicenti, Roberta Vacca, Lucrezia della Volpe, Sergio Arévalo, Kety Giannetti, Dafne Barozzi, Martina Franchino, Erika Zonari, Francesca Ferrua, Giacomo Farina, Chiara Brombin, Federica Cugnata, Martina Fiumara, Teresa Tavella, Leonardo Cherubin, Federico Fraschetta, Giulio Cerullo, Roberto Osellame, Marina Radrizzani, Samuele Ferrari, Ivan Merelli, Bernhard Gentner, Cristina Scielzo, Andrea Brendolan, Luigi Naldini, Alessandro Aiuti, Eugenio Montini, Manuela T. Raimondi, Raffaella Di Micco
Publié dans: Cell Stem Cell, Numéro 33, 2026, ISSN 1934-5909
Éditeur: Elsevier BV
DOI: 10.1016/J.STEM.2025.12.016

Donor insertion into <i>CX3CR1</i> allows epigenetic modulation of a constitutive promoter on hematopoietic stem cells and its activation upon myeloid differentiation

Auteurs: Iris Ramos-Hernández; Carla Fuster-García; Araceli Aguilar-González; María L Lozano-Vinagre; Guillermo Guenechea-Amurrio; Francisco J Sanchez-Luque; Manuel A F V Gonçalves; Toni Cathomen; Pilar Muñoz; Francisco J Molina-Estévez; Francisco Martín
Publié dans: Nucleic Acids Research, 2025, ISSN 1362-4962
Éditeur: Oxford University Press
DOI: 10.1093/NAR/GKAF344