Gene and Cell Therapy
One of our current research goals is to develop a gene editing strategy that combines viral and non-viral vectors to treat Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE), a rare disease due to inactivating mutations in the gene encoding thymidine phosphorylase, which has already demonstrated therapeutic efficacy in an animal model of the disease.
On the other hand, in collaboration with the Neuropediatrics group (Dra. F. Munell) and that of Dr. R. Hernández (University of Navarra), we are investigating another gene therapy approach based on high-capacity adenoviral vectors using a murine model of congenital muscular dystrophy type 1A (CMD1A).
Finally, in collaboration with the group of Dr. J. Verdaguer (University of Lleida), we are studying the mechanism of action, the cytolytic and pro-inflammatory activities, as well as several biomedical applications of a new family of peptides derived from intermediate filaments that were discovered by chance.
Team
Research lines
Gene therapy of congenital muscular dystrophy due to merosin deficiency
Development of a new gene therapy strategy based on high-capacity adenoviral vectors, which we carry out in collaboration with the group of Dr. Rubén Hernández, from the University of Navarra.
IP: Jordi Barquinero Mañez
Preclinical studies on gene therapy for Mitochondrial NeuroGastroIntestinal Encephalomyopathy (MNGIE)
IP: -
Tolerance induction by hematopoietic gene therapy targeting myeloid cells in a murine model of autoimmunity (EAE)
IP: -
Publications
Dysbiosis: An Indicator of COVID-19 Severity in Critically Ill Patients.
PMID: 36555453
Journal: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Year: 2022
Reference: Int J Mol Sci. 2022 Dec 13;23(24):15808. doi: 10.3390/ijms232415808.
Impact factor:
Publication type: Paper in international publication
Authors: Barquinero, Jordi; Cuenca, Silvia; Manichanh, Chaysavanh; Roca, Joaquim; Serrano-Gomez, Gerard; Sirvent, Jose-Maria; Soler, Zaida; Xie, Zixuan et al.
DOI: 10.3390/ijms232415808
Oxidative Stress in Structural Valve Deterioration: A Longitudinal Clinical Study.
PMID: 36358956
Journal: Biomolecules
Year: 2022
Reference: Biomolecules. 2022 Oct 31;12(11). pii: biom12111606. doi: 10.3390/biom12111606.
Impact factor:
Publication type: Paper in international publication
Authors: Badano, Luigi P; Barquinero, Jordi; Blasco-Lucas, Arnau; Casos, Kelly; Costa, Cristina; Cozzi, Emanuele; Evangelista, Arturo; Fellah-Hebia, Imen; Galinanes, Manuel; Galli, Cesare et al.
DOI: 10.3390/biom12111606
Preclinical assessment of a gene editing approach in a mouse model of Mitochondrial NeuroGastroIntestinal Encephalomyopathy.
PMID: 34498979
Journal: HUMAN GENE THERAPY
Year: 2021
Reference: Hum Gene Ther. 2021 Oct;32(19-20):1210-1223. doi: 10.1089/hum.2021.152.
Impact factor:
Publication type: Paper in international publication
Authors: Barquinero, Jordi; Borros, Salvador; Comes, Natalia; Fan, Steven H Y; Fornaguera, Cristina; Marti, Ramon; Oh, Sejin; Pares, Marta; Tam, Ying K; Vidal, Francisco et al.
DOI: 10.1089/hum.2021.152
Variable readthrough responsiveness of nonsense mutations in hemophilia A.
PMID: 31197069
Journal: HAEMATOLOGICA
Year: 2020
Reference: Haematologica. 2020 Jan 31;105(2):508-518. doi: 10.3324/haematol.2018.212118. Print 2020.
Impact factor:
Publication type: Paper in international publication
Authors: Barquinero, Jordi; Cortina, Vicente; Martorell, Lluis; Parra, Rafael; Vidal, Francisco et al.
DOI: 10.3324/haematol.2018.212118
Absence of p.R50X Pygm read-through in McArdle disease cellular models.
PMID: 31848135
Journal: Disease Models & Mechanisms
Year: 2020
Reference: Dis Model Mech. 2020 Jan 13;13(1). pii: dmm.043281. doi: 10.1242/dmm.043281.
Impact factor:
Publication type: Paper in international publication
Authors: Andreu, Antoni L; Arenas, Joaquin; Barquinero, Jordi; Brull, Astrid; de Luna, Noemi; Krag, Thomas O; Lucia, Alejandro; Martin, Miguel Angel; Moya, Laura; Pares, Marta et al.
DOI: 10.1242/dmm.043281
Absence of p.R50X Pygm read-through in McArdle disease cellular models.
PMID: 31848135
Journal: Disease Models & Mechanisms
Year: 2020
Reference: Dis Model Mech. 2020 Jan 13;13(1). pii: dmm.043281. doi: 10.1242/dmm.043281.
Impact factor: 4.651
Publication type: Paper in international publication
Authors: Tarraso, Guillermo, Real-Martinez, Alberto, Pares, Marta, Romero-Cortadellas, Lidia, Puigros, Laura, de Luna, Noemi, Brull, Astrid, Martin, Miguel Angel, Arenas, Joaquin, Lucia, Alejandro et al.
DOI: 10.1242/dmm.043281
Successful engraftment of gene-corrected hematopoietic stem cells in non-conditioned patients with Fanconi anemia.
PMID: 31501599
Journal: NATURE MEDICINE
Year: 2019
Reference: Nat Med. 2019 Sep;25(9):1396-1401. doi: 10.1038/s41591-019-0550-z. Epub 2019 Sep 9.
Impact factor:
Publication type: Paper in international publication
Authors: Alberquilla, Omaira; Alvarez, Lara; Barquinero, Jordi; Bogliolo, Massimo; Bueren, Juan A; Casado, Jose A; Catala, Albert; Cerrato, Laura; Diaz de Heredia, Cristina; Galvez, Eva et al.
DOI: 10.1038/s41591-019-0550-z
Expression of microRNA-155 in inflammatory cells modulates liver injury.
PMID: 29420849
Journal: HEPATOLOGY
Year: 2018
Reference: Hepatology. 2018 Aug;68(2):691-706. doi: 10.1002/hep.29833. Epub 2018 May 2.
Impact factor:
Publication type: Paper in international publication
Authors: Aguilar-Bravo, Beatriz; Barquinero, Jordi; Blaya, Delia; Caballeria, Juan; Casacuberta-Serra, Silvia; Coll, Mar; Cubero, Francisco Javier; Gines, Pere; Graupera, Isabel; Hao, Fengjie et al.
DOI: 10.1002/hep.29833
A reproducible method for the isolation and expansion of ovine mesenchymal stromal cells from bone marrow for use in regenerative medicine preclinical studies.
PMID: 27860364
Journal: Journal of Tissue Engineering and Regenerative Medicine
Year: 2017
Reference: J Tissue Eng Regen Med. 2017 Dec;11(12):3408-3416. doi: 10.1002/term.2254. Epub 2016 Nov 18.
Impact factor:
Publication type: Paper in international publication
Authors: Aguirre, Marius; Barquinero, Jordi; Batlle-Morera, Laura; Caminal, Marta; Garcia, Joan; Rabanal, Rosa Maria; Velez, Roberto; Vivas, Daniel; Vives, Joaquim et al.
DOI: 10.1002/term.2254
Advanced cell-based modeling of the royal disease: characterization of the mutated F9 mRNA.
PMID: 28834196
Journal: JOURNAL OF THROMBOSIS AND HAEMOSTASIS
Year: 2017
Reference: J Thromb Haemost. 2017 Nov;15(11):2188-2197. doi: 10.1111/jth.13808. Epub 2017 Sep 25.
Impact factor:
Publication type: Paper in international publication
Authors: Altisent, C; Barquinero, J; Borras, N; Casacuberta-Serra, S; Corrales, I; Dubart-Kupperschmitt, A; Follenzi, A; Jimenez-Delgado, S; Luce, E; Martorell, L et al.
DOI: 10.1111/jth.13808
Response of the human myocardium to ischemic injury and preconditioning: The role of cardiac and comorbid conditions, medical treatment, and basal redox status.
PMID: 28380047
Journal: PLoS One
Year: 2017
Reference: PLoS One. 2017 Apr 5;12(4):e0174588. doi: 10.1371/journal.pone.0174588. eCollection 2017.
Impact factor:
Publication type: Paper in international publication
Authors: Barquinero, Jordi; Blasco-Lucas, Arnau; Casos, Kelly; Castro, Miguel A; Ferrer-Curriu, Gemma; Galinanes, Manuel; Gracia-Baena, Juan Manuel; Perez, Maria L; Permanyer, Eduard; Soler-Ferrer, Paula et al.
DOI: 10.1371/journal.pone.0174588
Myeloid-derived suppressor cells can be efficiently generated from human hematopoietic progenitors and peripheral blood monocytes.
PMID: 28108746
Journal: IMMUNOLOGY AND CELL BIOLOGY
Year: 2017
Reference: Immunol Cell Biol. 2017 Jul;95(6):538-548. doi: 10.1038/icb.2017.4. Epub 2017 Jan 21.
Impact factor:
Publication type: Paper in international publication
Authors: Barquinero, Jordi; Casacuberta-Serra, Silvia; Coves, Elisabet; Espejo, Carmen; Golbano, Arantxa; Pares, Marta et al.
DOI: 10.1038/icb.2017.4
Myeloid-derived suppressor cells expressing a self-antigen ameliorate experimental autoimmune encephalomyelitis.
PMID: 27693617
Journal: EXPERIMENTAL NEUROLOGY
Year: 2016
Reference: Exp Neurol. 2016 Dec;286:50-60. doi: 10.1016/j.expneurol.2016.09.012. Epub 2016 Sep 28.
Impact factor:
Publication type: Paper in international publication
Authors: Barquinero, Jordi; Casacuberta-Serra, Silvia; Costa, Carme; Eixarch, Herena; Espejo, Carmen; Lopez-Estevez, Sergio; Mansilla, Maria Jose; Martorell, Lluis; Montalban, Xavier; Pares, Marta et al.
DOI: 10.1016/j.expneurol.2016.09.012
Long-term restoration of thymidine phosphorylase function and nucleoside homeostasis using hematopoietic gene therapy in a murine model of MNGIE.
PMID: 27004974
Journal: HUMAN GENE THERAPY
Year: 2016
Reference: Hum Gene Ther. 2016 Sep;27(9):656-67. doi: 10.1089/hum.2015.160. Epub 2016 May 4.
Impact factor:
Publication type: Paper in international publication
Authors: Andreu, Antoni L; Barba, Ignasi; Barquinero, Jordi; Cabrera-Perez, Raquel; Camara, Yolanda; Costa, Carme; de Luna, Noemi; Hirano, Michio; Marti, Ramon; Torres-Torronteras, Javier et al.
DOI: 10.1089/hum.2015.160
Molecular characterization of ten F8 splicing mutations in RNA isolated from patient's leucocytes: assessment of in silico prediction tools accuracy.
PMID: 25652415
Journal: HAEMOPHILIA
Year: 2015
Reference: Haemophilia. 2015 Mar;21(2):249-57. doi: 10.1111/hae.12562. Epub 2015 Feb 5.
Impact factor:
Publication type: Paper in international publication
Authors: Barquinero, J; Corrales, I; Martorell, L; Parra, R; Ramirez, L; Raya, A; Vidal, F et al.
DOI: 10.1111/hae.12562
Hematopoietic chimerisms: friends or foes?
PMID: 90001001
Journal: Advances in Regenerative Biology
Year: 2014
Reference: Advances in Regenerative Biology. 2014 Sept 25
Impact factor:
Publication type: Paper in international publication
Authors: Barquinero J; Casacuberta-Serra S; Martorell LL et al.
DOI: 10.3402/arb.v1.24429
Thymidine phosphorylase is both a therapeutic and a suicide gene in a murine model of mitochondrial neurogastrointestinal encephalomyopathy.
PMID: 24807807
Journal: GENE THERAPY
Year: 2014
Reference: Gene Ther. 2014 Jul;21(7):673-81. doi: 10.1038/gt.2014.41. Epub 2014 May 8.
Impact factor:
Publication type: Paper in international publication
Authors: Barquinero, J; Casacuberta-Serra, S; Ferrer, G; Hirano, M; Lopez-Estevez, S; Mansilla, M J; Marti, R; Martorell, L; Torres-Torronteras, J et al.
DOI: 10.1038/gt.2014.41
Anti-myelin antibodies play an important role in the susceptibility to develop proteolipid protein-induced experimental autoimmune encephalomyelitis.
PMID: 24188195
Journal: CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Year: 2014
Reference: Clin Exp Immunol. 2014 Feb;175(2):202-7. doi: 10.1111/cei.12233.
Impact factor:
Publication type: Paper in international publication
Authors: Alvarez-Cermeno, J C; Eixarch, H; Espejo, C; Guaza, C; Mansilla, M J; Marin, N; Mecha, M; Montalban, X; Rodriguez-Martin, E; Villar, L M et al.
DOI: 10.1111/cei.12233
Hsp70 regulates immune response in experimental autoimmune encephalomyelitis.
PMID: 25153885
Journal: PLoS One
Year: 2014
Reference: PLoS One. 2014 Aug 25;9(8):e105737. doi: 10.1371/journal.pone.0105737. eCollection 2014.
Impact factor:
Publication type: Paper in international publication
Authors: Aigrot, Marie-Stephane; Castillo, Mireia; Costa, Carme; Eixarch, Herena; Espejo, Carmen; Lubetzki, Catherine; Mansilla, M Jose; Martin, Roland; Montalban, Xavier; Tepavcevic, Vanja et al.
DOI: 10.1371/journal.pone.0105737
Next-generation scholarly communication: A researcher’s perspective
PMID: 28800000
Journal: INTERNATIONAL MICROBIOLOGY
Year: 2013
Reference: International Microbiology (2013) 16:253-257
Impact factor:
Publication type: Paper in international publication
Authors: Barquinero Mañez, Jordi et al.
DOI: 10.2436/20.1501.01.201
Bone marrow transplantation in dysferlin deficient mice results in a mild functional improvement.
PMID: 23777246
Journal: STEM CELLS AND DEVELOPMENT
Year: 2013
Reference: Stem Cells Dev. 2013 Nov 1;22(21):2885-94. doi: 10.1089/scd.2013.0049. Epub 2013 Jul 26.
Impact factor:
Publication type: Paper in international publication
Authors: Barquinero, Jordi; Diaz-Manera, Jordi; Flix, Barbara; Gallardo, Eduard; Illa, Isabel; Mancuso, Renzo; Navarro, Xavier; Navas-Madronal, Miquel; Santos-Nogueira, Eva; Suarez-Calvet, Xavier et al.
DOI: 10.1089/scd.2013.0049
Inhibition of delta-like ligand 4 decreases Th1/Th17 response in a mouse model of multiple sclerosis.
PMID: 23466692
Journal: NEUROSCIENCE LETTERS
Year: 2013
Reference: Neurosci Lett. 2013 Apr 29;541:161-6. doi: 10.1016/j.neulet.2013.02.038. Epub 2013 Mar 1.
Impact factor:
Publication type: Paper in international publication
Authors: Costa, Carme; Eixarch, Herena; Espejo, Carmen; Godessart, Nuria; Kunkel, Steve L; Mansilla, M Jose; Montalban, Xavier et al.
DOI: 10.1016/j.neulet.2013.02.038
Notch signals contribute to preserve the multipotentiality of human CD34(+)CD38(-)CD45RA(-)CD90(+) hematopoietic progenitors by maintaining T cell lineage differentiation potential.
PMID: 22981934
Journal: EXPERIMENTAL HEMATOLOGY
Year: 2012
Reference: Exp Hematol. 2012 Dec;40(12):983-993.e4. doi: 10.1016/j.exphem.2012.08.009. Epub 2012 Sep 11.
Impact factor:
Publication type: Paper in international publication
Authors: Azqueta, Carmen; Barquinero, Jordi; Gimeno, Ramon; Gomez, Alba; Pereira-Mendez, Sonia; Querol, Sergi; Sanchez-Dominguez, Rebeca; Torrabadella, Marta et al.
DOI: 10.1016/j.exphem.2012.08.009
Treatment with MOG-DNA vaccines induces CD4+CD25+FoxP3+ regulatory T cells and upregulates genes with neuroprotective functions in experimental autoimmune encephalomyelitis.
PMID: 22727044
Journal: Journal of Neuroinflammation
Year: 2012
Reference: J Neuroinflammation. 2012 Jun 22;9:139. doi: 10.1186/1742-2094-9-139.
Impact factor:
Publication type: Paper in international publication
Authors: ; ; ; ; ; ; ; ; et al.
DOI: 10.1186/1742-2094-9-139
Heat Shock Protein 70: Roles in Multiple Sclerosis.
PMID: 22669475
Journal: MOLECULAR MEDICINE
Year: 2012
Reference: Mol Med. 2012 Sep 7;18:1018-28. doi: 10.2119/molmed.2012.00119.
Impact factor:
Publication type: Review in international publication
Authors: ; ; et al.
DOI: 10.2119/molmed.2012.00119
Myeloid-derived suppressor cells (MDSC): Another play in the orchestra
PMID: 90000002
Journal:
Year: 2011
Reference: Inmunologia. 2011; 30: 45-53
Impact factor:
Publication type: Letter or abstract
Authors: ; et al.
DOI:
Implication of the toll-like receptor 4 pathway in the response to interferon-beta in multiple sclerosis.
PMID: 22028223
Journal: ANNALS OF NEUROLOGY
Year: 2011
Reference: Ann Neurol. 2011 Oct;70(4):634-45. doi: 10.1002/ana.22511.
Impact factor:
Publication type: Paper in international publication
Authors: Angeles Moro, Maria; Bustamante, Marta F; Carmen Edo, Mari; Comabella, Manuel; Costa, Carme; Espejo, Carmen; Fissolo, Nicolas; Lizasoain, Ignacio; Mansilla, Maria Jose; Montalban, Xavier et al.
DOI: 10.1002/ana.22511
Hematopoietic gene therapy restores thymidine phosphorylase activity in a cell culture and a murine model of MNGIE.
PMID: 21451581
Journal: GENE THERAPY
Year: 2011
Reference: Gene Ther. 2011 Aug;18(8):795-806. doi: 10.1038/gt.2011.24. Epub 2011 Mar 31.
Impact factor:
Publication type: Paper in international publication
Authors: ; ; ; ; ; ; ; ; et al.
DOI: 10.1038/gt.2011.24
Dendritic and tumor cell fusions transduced with adenovirus encoding CD40L eradicate B-cell lymphoma and induce a Th17-type response.
PMID: 20010627
Journal: GENE THERAPY
Year: 2010
Reference: Gene Ther. 2010 Apr;17(4):469-77. Epub 2009 Dec 10.
Impact factor:
Publication type: Paper in international publication
Authors: Alvarez, E; Barquinero, J; Briones, J; Moga, E; Sierra, J et al.
DOI: 10.1038/gt.2009.150
Bone marrow transplantation induces normoglycemia in a type 2 diabetes mellitus murine model.
PMID: 19715898
Journal: TRANSPLANTATION PROCEEDINGS
Year: 2009
Reference: Transplant Proc. 2009 Jul-Aug;41(6):2282-5.
Impact factor:
Publication type: Paper in international publication
Authors: Barquinero, J; Cruzado, J M; Flaquer, M; Franquesa, M; Grinyo, J M; Gutierrez, C; Lloberas, N; Torras, J et al.
DOI: 10.1016/j.transproceed.2009.06.034
Tolerance induction in experimental autoimmune encephalomyelitis using non-myeloablative hematopoietic gene therapy with autoantigen.
PMID: 19277013
Journal: MOLECULAR THERAPY
Year: 2009
Reference: Mol Ther. 2009 May;17(5):897-905.
Impact factor:
Publication type: Paper in international publication
Authors: Barquinero, Jordi; Castillo, Mireia; Eixarch, Herena; Espejo, Carmen; Gimeno, Ramon; Gomez, Alba; Mansilla, Maria Jose; Mildner, Alexander; Montalban, Xavier; Prinz, Marco et al.
DOI: 10.1038/mt.2009.42
Transgene expression levels determine the immunogenicity of transduced hematopoietic grafts in partially myeloablated mice.
PMID: 19707185
Journal: MOLECULAR THERAPY
Year: 2009
Reference: Mol Ther. 2009 Nov;17(11):1904-9.
Impact factor:
Publication type: Paper in international publication
Authors: Barquinero, Jordi; Eixarch, Herena; Espejo, Carmen; George, Monica; Gimeno, Ramon; Gomez, Alba; Kadar, Elisabeth; Martinez, Nuria; Petriz, Jordi et al.
DOI: 10.1038/mt.2009.198
Identification of multipotent mesenchymal stromal cells in the reactive stroma of a prostate cancer xenograft by side population analysis.
PMID: 19447103
Journal: EXPERIMENTAL CELL RESEARCH
Year: 2009
Reference: Exp Cell Res. 2009 Oct 15;315(17):3004-13.
Impact factor:
Publication type: Paper in international publication
Authors: Barbosa-Desongles, Anna; Barquinero, Jordi; Hurtado, Antoni; Morote, Joan; Munell, Francina; Pinos, Tomas; Poupon, Marie-France; Reventos, Jaume; Santamaria-Martinez, Albert; Seoane, Joan et al.
DOI: 10.1016/j.yexcr.2009.05.007
Estrogen receptor beta displays cell cycle-dependent expression and regulates the G1 phase through a non-genomic mechanism in prostate carcinoma cells.
PMID: 18607069
Journal: CELLULAR ONCOLOGY
Year: 2008
Reference: Cell Oncol. 2008;30(4):349-65.
Impact factor:
Publication type: Paper in international publication
Authors: Barbosa-Desongles, Anna; Barquinero, Jordi; Bellmunt, Joaquim; de Torres, Ines; Hurtado, Antoni; Lopez-Aviles, Sandra; Morote, Joan; Munell, Francina; Petriz, Jordi; Pinos, Tomas et al.
DOI:
Thesis
Desenvolupament de noves estratègies terapéutiques per les distròfies musculars
PhD student:
Penelope Romero Duque
Director/s:
Francina Munell Casadesus, Jordi Barquinero Mañez
University: Universidad Autònoma de Barcelona
Year: 2022
Preclinical assessment of a gene editing approach for MNGIE
PhD student:
Marta Parés Casellas
Director/s:
Jordi Barquinero Mañez
University: Universidad Autònoma de Barcelona
Year: 2020
Antigen-specific MDSCs induce immunological tolerance in an experimental model of multiple sclerosis. Generation of human MDSCs from hematopoietic progenitors as a therapeutic tool
PhD student:
Silvia Casacuberta Serra
Director/s:
Jordi Barquinero Mañez, Carmen Espejo Ruiz
University: Universidad Autònoma de Barcelona
Year: 2016
Estudio de los mecanismos terapéuticos en la inducción de tolerancia inmunológica en un modelo animal de esclerosis múltiple
PhD student:
Alba Gomez Morago
Director/s:
Jordi Barquinero Mañez, Carmen Espejo Ruiz
University: Universidad Autònoma de Barcelona
Year: 2012
Estudios preclínicos de terapia génica basada en células madre hematopoyéticas para el MNGIE
PhD student:
Javier Torres Torronteras
Director/s:
Ramon Martí Seves, Jordi Barquinero Mañez
University: Universidad Autònoma de Barcelona
Year: 2011
News
Over the course of two days, experts presented the latest advances in vectors, different gene modification techniques and their transfer to clinical practice.