Nuestros investigadores

Oihana Murillo Sauca

Publicaciones científicas más recientes (desde 2010)

Autores:  et al.
Revista: HEPATOLOGY
ISSN 0270-9139  Vol. 70  Nº 1  2019  págs. 108 - 126
Gene therapy with an adeno-associated vector (AAV) serotype 8 encoding the human ATPase copper-transporting beta polypeptide (ATP7B) complementary DNA (cDNA; AAV8¿ATP7B) is able to provide long-term copper metabolism correction in 6-week-old male Wilson disease (WD) mice. However, the size of the genome (5.2 kilobases [kb]) surpasses the optimal packaging capacity of the vector, which resulted in low-yield production; in addition, further analyses in WD female mice and in animals with a more advanced disease revealed reduced therapeutic efficacy, as compared to younger males. To improve efficacy of the treatment, an optimized shorter AAV vector was generated, in which four out of six metal¿binding domains (MBDs) were deleted from the ATP7B coding sequence, giving rise to the miniATP7B protein (delta57-486-ATP7B). In contrast to AAV8-ATP7B, AAV8-miniATP7B could be produced at high titers and was able to restore copper homeostasis in 6- and 12-week-old male and female WD mice. In addition, a recently developed synthetic AAV vector, AAVAnc80, carrying the miniATP7B gene was similarly effective at preventing liver damage, restoring copper homeostasis, and improving survival 1 year after treatment. Transduction of approximately 20% of hepatocytes was sufficient to normalize copper homeostasis, suggesting that corrected hepatocytes are acting as a sink to eliminate excess of copper.
Autores: Benichou, B.; Collantes M; et al.
Revista: MOLECULAR THERAPY
ISSN 1525-0016  Vol. 27  Nº 4  2019  págs. 197 - 198
Autores:  et al.
Revista: JOURNAL OF HEPATOLOGY (ONLINE)
ISSN 0168-8278  Vol. 68  Nº 5  2018  págs. 1088 - 1090
Autores: González-Aseguinolaza, Gloria; et al.
Revista: MOLECULAR THERAPY
ISSN 1525-0016  Vol. 26  Nº 5  2018  págs. 388 - 388
Autores: González-Aseguinolaza, Gloria; et al.
Revista: MOLECULAR THERAPY
ISSN 1525-0016  Vol. 26  Nº 5  2018  págs. 249 - 250
Autores:  et al.
Revista: JOURNAL OF HEPATOLOGY (ONLINE)
ISSN 0168-8278  Vol. 68  Nº Supl. 1  2018  págs. S83 - S83
Autores:  et al.
Revista: MOLECULAR THERAPY
ISSN 1525-0016  Vol. 25  Nº 5 - Supl.1  2017  págs. 188 - 188
Autores:  et al.
Revista: JOURNAL OF HEPATOLOGY (ONLINE)
ISSN 0168-8278  Vol. 66  Nº 1  2017  págs. S5 - S6
Autores:  et al.
Revista: JOURNAL OF HEPATOLOGY
ISSN 1600-0641  Vol. 64  Nº 2  2016  págs. 419-26
Our data demonstrate that AAV8-AAT-ATP7B-mediated gene therapy provides long-term correction of copper metabolism in a clinically relevant animal model of WD providing support for future translational studies.
Autores: Azpilicueta, Arantza; et al.
Revista: JOURNAL OF IMMUNOLOGY
ISSN 0022-1767  Vol. 190  Nº 12  2013  págs. 6694 - 6706
Agonist anti-CD137 (4-1BB) mAbs enhance CD8-mediated antitumor immunity. Agonist anti-human CD137 mAbs binding to four distinct epitopes on the CD137 glycoprotein costimulated T cell activation irrespective of the engaged epitope or its interference with CD137L binding. CD137 perturbation with all these agonist mAbs resulted in Ag and Ab internalization toward an endosomal vesicular compartment. Internalization was observed in activated T lymphocytes from humans and mice, not only in culture but also in Ab-injected living animals. These in vivo experiments were carried out upon systemic i.v. injections with anti-CD137 mAbs and showed CD137 internalization in tumor-infiltrating lymphocytes and in activated human T cells transferred to immunodeficient mice. Efficient CD137 internalization required K63 polyubiquitination and endocytosed CD137-containing vesicles recruited TNFR-associated factor (TRAF) 2 and were decorated with K63 polyubiquitins. CD137 stimulation activates NF-¿B through a K63-linked polyubiquitination-dependent route, and CD137-associated TRAF2 becomes K63 polyubiquitinated. Consistent with a role for TRAF2 in CD137 signaling, transgenic mice functionally deficient in TRAF2 showed delayed immunotherapeutic activity of anti-CD137 mAbs. As a whole, these findings advance our knowledge of the mechanisms of action of anti-CD137 immunostimulatory mAbs such as those currently undergoing clinical trials in cancer patients.
Autores: Garasa, S; et al.
Revista: FASEB JOURNAL
ISSN 0892-6638  Vol. 26  Nº 8  2012  págs. 3380 - 3392
Autores: Ochoa, María del Carmen; Duitman, E. H.; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 7  Nº 12  2012 
Apolipoprotein A-I (Apo A-I) is a major component of high density lipoproteins (HDL) that transport cholesterol in circulation. We have constructed an expression plasmid encoding a chimeric molecule encompassing interleukin-15 (IL-15) and Apo A-I (pApo-hIL15) that was tested by hydrodynamic injections into mice and was co-administered with a plasmid encoding the sushi domain of IL-15R alpha (pSushi) in order to enhance IL-15 trans-presentation and thereby bioactivity. The pharmacokinetics of the Apo A-I chimeric protein were much longer than non-stabilized IL-15 and its bioactivity was enhanced in combination with IL-15R alpha Sushi. Importantly, the APO-IL-15 fusion protein was incorporated in part into circulating HDL. Liver gene transfer of these constructs increased NK and memory-phenotype CD8 lymphocyte numbers in peripheral blood, spleen and liver as a result of proliferation documented by CFSE dilution and BrdU incorporation. Moreover, the gene transfer procedure partly rescued the NK and memory T-cell deficiency observed in IL-15R alpha(-/-) mice. pApo-hIL15+ pSushi gene transfer to the liver showed a modest therapeutic activity against subcutaneously transplanted MC38 colon carcinoma tumors, that was more evident when tumors were set up as liver metastases. The improved pharmacokinetic profile and the strong biological activity of APO-IL-15 fusion protein holds promise for further development in combination with other immunotherapies.
Autores: Ochoa, María del Carmen; Arina, A.; et al.
Revista: GENE THERAPY
ISSN 0969-7128  Vol. 17  Nº 5  2010  págs. 687 - 689