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The work done by our team within the CIBERER and through collaboration with other CIBERER groups and Linked Clinical Groups (H . Niño Jesus and H . Vall d’Hebron), is allowing us to lead global gene therapy programs in AF, and trust also do so in other rare diseases that affect blood cells . At the same time we offer collaboration to our CIBERER collaborators for the development of new advanced therapies for rare diseases .
Most relevant scientific articles
• leon-rico D, alDea m, sancHez r, seGoVia Jc, Weiss la, HiDalGo a, et al . Brief report: reduced expression of CD18 leads to the in vivo expansion of hematopoietic stem cells in mouse bone marrow . Stem cells . 2014 Oct;32(10):2794-8 . PubMed PMID: 24906078 .
• rio p, banos r, lombarDo a, quintana-bustamante o, alVarez l, Garate z, et al . Targeted gene therapy and cell reprogramming in Fanconi anemia . EMBO molecular medicine . 2014 Jun;6(6):835-48 . PubMed PMID: 24859981 . Pubmed Central PMCID: 4203359 .
• naVarro s, moleiro V, molina-esteVez FJ, lozano ml, cHincHon r, almarza e, et al . Generation of iPSCs from ge- netically corrected Brca2 hypomorphic cells: implications in cell reprogramming and stem cell therapy . Stem cells . 2014 Feb;32(2):436-46 . PubMed PMID: 24420904 .
• pulecio J, niVet e, sancHo-martinez i, Vitaloni m, GuenecHea G, xia y, et al . Conversion of human fibroblasts into monocyte-like progenitor cells . Stem cells . 2014 Nov;32(11):2923-38 . PubMed PMID: 25175072 . Pubmed Central PMCID: 4198469 .
• liu GH, suzuKi K, li m, qu J, montserrat n, tarantino c, et al . Modelling Fanconi anemia pathogenesis and the- rapeutics using integration-free patient-derived iPSCs . Nature communications . 2014;5:4330 . PubMed PMID: 24999918 . Pubmed Central PMCID: 4291073
Highlights
As a result of gene complementation studies performed in our laboratory and in collaboration with the team of Dr . Surrallés (U745), we described the XPF/ERCC4 gene as a new gene involved in Fanconi anemia pathway, known as the FANCQ gene (Bogliolo et al, 2014) . Thanks to the Orphan Drug designation to our lentiviral vector PGK-FANCA-WPRE, we obtained funding for the development of the first clinical trial of lentiviral gene therapy of hematopoietic stem cells mobilized in patients with FA subtype A and in 2014, the IMPD was approved for the manufacture of the gene therapy cellular drug .
We have shown that gene edition on FA cells is possible and those cells were reprogrammed to generate iPSCs, which later were differentiated into the hematopoietic lineage (Rio et al . EMBO Mol Med 2014 Dew Thesis Bathrooms 2014) . In a similar work done in Fanca-/- mouse cells, we demonstrated the advantages and limitations of cellular reprogramming techniques for the development of hematopoietic cell therapy protocols (Navarro et al Stem Cells 2014) .
In the field of PKD anemia, genetically edited iPSCs derived from two patients with this deficiency have been described . The gene modification was performed by homologous recombination enhanced by TALE nucleases (Thesis Zita Garate 2014) . In August 2014 one of our lentiviral vectors was designated as a new orphan drug for the treatment of PKD (EU / 3/14/1130) .
In 2014 it has been possible to complete the development of four lentiviral vectors candidates for the treatment of leukocyte adhesion deficiency type I . These vectors have been tested in vitro and in vivo, using different models of the disease, and have proved to be effective to correct the disease phenotype in both human and mouse cells (Leon et al . Stem Cells 2014) .
Institution: Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) Contact: CIEMAT · Avenida Complutense, 40 . 28040 Madrid Phone: (+34) 91 346 65 18 · Website: http://www .ciemat .es
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