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Most relevant s naVarro, V Moleiro, F.J. Molina-esteVez, M.l. lozano, r chinchon, e alMarza, o quintana-
bustaMante, G MostoslaVsky, t MaetziG, M Galla, n heinz, b schiedlMeier, y torres, u Modlich,
scientific e s, P r, J.c. s, a r, G G, J.c. i-b J.a. b. Ge-
aMPeríoeGoViaayaüenecheazPisuaelMonteand ueren
articles
neration of iPSCs from genetically corrected Brca2 hypomorphic cells: Implications in cell
reprogramming and stem cell therapy. Stem Cells. Accepted manuscript online: 29 OCT

2013. DOI: 10.1002/stem.1586.
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oViedo a, yañez r, colMenero i, aldea M, rubio a, bueren Ja, laMana Ml. Reduced efficacy of
mesenchymal stromal cells in preventing graft-versus-host disease in an in vivo model of
haploidentical bone marrow transplant with leukemia. Cell Transplant. 2013;22(8):1381-

94. doi: 10.3727/096368912X657666. Epub 2012 Oct 4.

• Molina-esteVez FJ, lozano Ml, naVarro s, torres y, GrabundziJa i, iVics z, saMPer e, bueren Ja,
Guenechea G. Impaired cell reprogramming in non homologous end joining deficient cells.

Stem Cells. 2013 Aug;31(8):1726-30. doi: 10.1002/stem.1406.
• b M, s b, s c, d b, s y, r a, t JP, M J, r
oGliolochustertoePkererkuntuaaMsruJilloinGuillónaMírez
MJ, PuJol r, casado Ja, baños r, rio P, knies k, zúñiGa s, benítez J, bueren Ja, JasPers nG, ä
s od, W JP, s d, s J. Mutations in ERCC4, encoding the DNA-
chrerde interchindlerurrallés
repair endonuclease XPF, cause Fanconi anemia. Am J Hum Genet. 2013 May 2;92(5):800-
6. doi: 10.1016/j.ajhg.2013.04.002. Epub 2013 Apr 25.

• treMblay JP, Xiao X, aartsMa-rus a, barbas c, blau hM, boGdanoVe aJ, boycott k, braun s,
b Xo, b Ja, b M, b bJ, c M, c t, c J, c
reakeFielduerenuschMannyrnealosathoMenhaMberlainhuah
M, cornetta k, daVies ke, dickson JG, duchateau P, Flotte tr, Gaudet d, Gersbach ca, Gilbert
r, Glorioso J, herzoG rW, hiGh ka, huanG W, huard J, JounG Jk, liu d, liu d, lochMüller h,

lustiG l, Martens J, Massie b, MaVilio F, Mendell Jr, nathWani a, Ponder k, Porteus M, PuyMirat J,
saMulski J, takeda s, thrasher a, Vandendriessche t, Wei y, Wilson JM, Wilton sd, WolFe Jh, Gao
G. Translating the genomics revolution: the need for an international gene therapy consor-

tium for monogenic diseases. Mol Ther. 2013 Feb;21(2):266-8. doi: 10.1038/mt.2013.4.

This research line is focused on the development of novel therapies for rare disea-
Highlights
ses affecting the lympho-hematopoietic system. During 2013 we have progressed our

studiesanemiaFanconianemia, erythrocytepyruvatekinasedeficiency,andprimary
immunodeficiency LAD- 1.

Among the most significant results obtained during 2013 we have verified the efficacy

and safety of gene therapy protocols with a lentiviral vector designed in our laboratory
for the treatment of Fanconi anemia. Also we have analysed the involvement of the

NHEJ repair pathway in the reprogramming of adult cells to generate induced pluri-

potent stem cells (iPSCs). These studies have facilitated the development of a clinical
trial for the gene therapy of Fanconi anemia, and have provided a new tool for unders-

tandingtheroleofNHEJincellreprogramming. AlsorelatedwiththeFanconianemia
studies, we have generated for the first time gene corrected iPSCs from mice deficient

in the BRCA2/FANCD1 gene, and have collaborated with the team of J. Surralles in
the discovery of a new Fanconi anemia gene , and developed new transposons for the

treatment of this disease.
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Regarding the studies on the erythrocyte pyruvate kinase deficiency anemia, we have 20
T
demonstrated the effectiveness of gene editing tools (TALE nuclease) for the genera- OR
tion of iPSCs from these patients. This allowed us to perform gene correction by homo- P
RE
logous recombination in erythrocyte pyruvate kinase deficient cells. Finally, we have L
completed the development of a lentiviral vector for the treatment of pyruvate kinase A
NU
deficiency by gene therapy, and will ask a designation of an Orphan Drug designation N
in the near future.
A
R /
In the field of LAD-I immunodeficiency, the relevance of CD18 in hematopoietic stem E
ER
cell function has been investigated using a mouse model of the disease. Additionally, B
CI
a family of lentiviral vectors have been generated, whose functionality is under eva-
luation.
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