Lombardia

Group Leader : Anna Villa

+390226433592 | anna.villa@cnr.it

URL (group home page)

https://www.itb.cnr.it/https://irgb.cnr.it/
https://research.hsr.it/en/institutes/san-raffaele-telethon-institute-for-gene-therapy/pathogenesis-and-treatment-of-immune-and-bone-diseases.html

Institute

Institute for Biomedical Technologies (ITB)
Via Fratelli Cervi, 93 20054 Segrate (MI), Italy

Institute for Genetic and Biomedical Research (IRGB)– Milan Unit
Via Fantoli 15/16 – 20090 Milan (MI), Italy

Group/Lab members

Valentina Capo valentina.capo@cnr.it
Maria Carmina Castiello mariacarmina.castiello@cnr.it

Activities

• Study of the pathogenesis and treatment of immune diseases (RAG1 and RAG2 genetic defects, Omenn Syndrome, Wiskott-Aldrich Syndrome, HyperIgM syndrome, WHIM syndrome, mucopolysaccharidosis) and bone diseases (autosomal recessive osteopetrosis). Our treatment approaches include gene therapy, genome editing and base editing.
• Optimization of novel conditioning regimens based on the use of biological compounds and hematopoietic stem/progenitor cell mobilization drugs to minimize toxicity.
• Elucidation of pathogenetic basis of autoimmune manifestations in thymoma

Key words

CRISPR-Cas9, lentiviral vectors, adenine base editing, hematopoietic stem cells, osteoclasts

Key publications

1. Correction of osteopetrosis in the neonate oc/oc murine model after lentiviral vector gene therapy and non-genotoxic conditioning. Penna S, Zecchillo A, Di Verniere M, Fontana E, Iannello V, Palagano E, Mantero S, Cappelleri A, Rizzoli E, Santi L, Crisafulli L, Filibian M, Forlino A, Basso-Ricci L, Scala S, Scanziani E, Schinke T, Ficara F, Sobacchi C, Villa A, Capo V. Front Endocrinol (Lausanne). 2024 Sep 9;15:1450349. doi: 10.3389/fendo.2024.1450349. eCollection 2024. PMID: 39314524
2. Exonic knockout and knockin gene editing in hematopoietic stem and progenitor cells rescues RAG1 immunodeficiency. Castiello MC, Brandas C, Ferrari S, Porcellini S, Sacchetti N, Canarutto D, Draghici E, Merelli I, Barcella M, Pelosi G, Vavassori V, Varesi A, Jacob A, Scala S, Basso Ricci L, Paulis M, Strina D, Di Verniere M, Sergi Sergi L, Serafini M, Holland SM, Bergerson JRE, De Ravin SS, Malech HL, Pala F, Bosticardo M, Brombin C, Cugnata F, Calzoni E, Crooks GM, Notarangelo LD, Genovese P, Naldini L, Villa A. Sci Transl Med. 2024 Feb 7;16(733):eadh8162. doi: 10.1126/scitranslmed.adh8162. Epub 2024 Feb 7. PMID: 38324638
3. Partial correction of immunodeficiency by lentiviral vector gene therapy in mouse models carrying Rag1 hypomorphic mutations. Castiello MC, Di Verniere M, Draghici E, Fontana E, Penna S, Sereni L, Zecchillo A, Minuta D, Uva P, Zahn M, Gil-Farina I, Annoni A, Iaia S, Ott de Bruin LM, Notarangelo LD, Pike-Overzet K, Staal FJT, Villa A, Capo V. Front Immunol. 2023 Nov 13;14:1268620. doi: 10.3389/fimmu.2023.1268620. eCollection 2023. PMID: 38022635
4. Unbiased assessment of genome integrity and purging of adverse outcomes at the target locus upon editing of CD4+ T-cells for the treatment of Hyper IgM1. Canarutto D, Asperti C, Vavassori V, Porcellini S, Rovelli E, Paulis M, Ferrari S, Varesi A, Fiumara M, Jacob A, Sergi Sergi L, Visigalli I, Ferrua F, González-Granado LI, Lougaris V, Finocchi A, Villa A, Radrizzani M, Naldini L. EMBO J. 2023 Dec 1;42(23):e114188. doi: 10.15252/embj.2023114188. Epub 2023 Nov 2. PMID: 37916874
5. HyperIgE in hypomorphic recombination-activating gene defects. Castiello MC, Brandas C, Capo V, Villa A. Curr Opin Immunol. 2023 Feb;80:102279. doi: 10.1016/j.coi.2022.102279. Epub 2022 Dec 16.

Instruments/Technologies

Lentiviral transduction, CRISPR-Cas9 editing (viral and non viral delivery), adenine-base editing, lipid nanoparticles (LNPs), mouse models, multiparametric flow cytometry, human/murine hematopoietic stem and progenitor cell culture, lymphocyte functional assays, molecular assays (vector copy number, homologous directed repair and non-homologous end joining)