Gene transfer into stem cell
Unit major interests are in the field of hematopoietic stem cell biology and gene transfer to treat genetic diseases. Gene therapy is a therapeutic technique by which a functioning gene is inserted into the somatic cells of a patient to correct a genetic error or to provide a new function to the cell. Since 1989 the unit pioneered the use of viral vector-mediated gene transfer for gene therapy of human genetic diseases.
The group developed lentiviral vectors for the transcriptionally regulated expression of human beta-globin to correct hemoglobinopathies and they are leading a clinical trial of gene therapy for beta-thalassemia. Molecular studies will provide insight into human erythropoiesis and hematopoiesis.
Other projects include the study of vector-genome interaction, hematopoietic stem cell biology, hematopoietic stem cell-niche interactions and molecular control of erythropoiesis.
Ferrari G, Cavazzana M, Mavilio F. Gene therapy approaches to hemoglobinopathy. Hematol Oncol Clin N Am. 2017 Oct;31(5):835-852.
Zonari E, Desantis G, Petrillo C, Boccalatte FE, Lidonnici MR, Kajaste-Rudnitski A, Aiuti A, Ferrari G, Naldini L, Gentner B. Efficient ex vivo engineering and expansion of highly purified human hematopoietic stem/progenitor cell populations for gene therapy. Stem Cell Reports 2017 Apr 11;8(4):977-990.
Lidonnici MR, Aprile A, Frittoli MC, Mandelli G, Paleari Y, Spinelli A, Gentner B, Zambelli M, Parisi C, Bellio L, Cassinerio E, Zanaboni L, Cappellini MD, Ciceri F, Marktel S, Ferrari G. Plerixafor and G-CSF combination mobilizes hematopoietic stem and progenitors cells with a distinct transcriptional profile and a reduced in vivo homing capacity compared to Plerixafor alone. Haematologica 2017; 102(4):e120-e124.
Aprile A, Passerini G, Cappellini MD, Marktel S, Ciceri F, Ferrari G, Ceriotti F. When diagnostics meets translational research: detection of hemaglobin fractions in cellular lysates from in vitro erythroid cultures by Capillarys2 Flex Piercing analyzer (Sebia). Transl Res. 2016; 169: 31-39.e4.
Nai A, Lidonnici MR, Rausa M, Mandelli G, Pagani A, Silvestri L, Ferrari G, Camaschella C. The second transferrin receptor regulates red blood cell production in mice. Blood 2015; 125:1170-1179.
Moiani A, Paleari Y, Sartori D, Mezzadra R, Miccio A, Cattoglio C, Cocchiarella F, Lidonnici MR, Ferrari G*, Mavilio F*. Lentiviral vector integration in the human genome induces alternative splicing and generates aberrant transcripts. J Clin Invest. 2012 May; 122(5):1653-66. (* Corresponding authors)
Nai A, Pagani A, Mandelli G, Lidonnici MR, Silvestri L, Ferrari G, Camaschella C. Deletion of Tmprss6 attenuates the phenotype in a mouse model of ß-thalassemia. Blood 2012 May 24;119(21):5021-9.
Miccio A, Poletti V, Tiboni F, Rossi C, Antonelli A, Mavilio F, Ferrari G. The GATA1-HS2 enhancer allows persistent and position- independent expression of a ß-globin transgene. PLoS ONE 2011; 6(12):e27955.
Roselli EA, Mezzadra R, Frittoli MC, Maruggi G, Biral E, Mavilio F, Mastropietro F, Amato A, Tonon G, Refaldi C, Cappellini MD, Andreani M, Lucarelli G, Roncarolo MG, Marktel S, Ferrari G. Correction of ß- thalassemia major by gene transfer in hematopoietic progenitors of pediatric patients. EMBO Mol Med. 2010; 2:315-328.
Xynos A, Corbella P, Belmonte N, Zini R, Manfredini R, Ferrari G. Bone marrow-derived hematopoietic cells undergo myogenic differentiation following a Pax-7 independent pathway. Stem Cells. 2010; 28:965-973
Miccio A, Cesari R, Lotti F, Rossi C, Sanvito F, Ponzoni M, Routledge SJ, Chow CM, Antoniou MN, Ferrari G. In vivo selection of genetically modified erythroblastic progenitors leads to long-term correction of beta-thalassemia. Proc Natl Acad Sci. 2008; 105:10547-10552.
Mavilio F, Ferrari G. Genetic modification of somatic stem cells. The progress, problems and prospects of a new therapeutic technology. EMBO Rep. 2008; S64-69.