000098333 001__ 98333
000098333 005__ 20210126163933.0
000098333 0248_ $$2sideral$$a122076
000098333 037__ $$aART-2019-122076
000098333 041__ $$aeng
000098333 100__ $$aNieto-Romero, V.
000098333 245__ $$aSpecific gene correction of the AGXT gene and direct cell reprogramming for the treatment of Primary Hyperoxaluria Type 1
000098333 260__ $$c2019
000098333 5060_ $$aAccess copy available to the general public$$fUnrestricted
000098333 5203_ $$aP428
Primary Hyperoxaluria Type 1 (PH1) is an inherited rare metabolic liver disease caused by the deficiency in the alanine: glyoxylate aminotransferase enzyme (AGXT), involved in the glyoxylate metabolism. The only potentially curative treatment is organ transplantation. Thus, the development of new therapeutic approaches for the treatment of these patients appears as a priority.We propose the combination of site-specific gene correction and direct cell reprogramming for the generation of autologous phenotypically healthy induced hepatocytes (iHeps) from skin-derived fibroblast of PH1 patients. For the correction of AGXT mutations, we have designed specific gene editing tools to address gene correction by two different strategies, assisted by CRISPR/Cas9 system. Accurate specific point mutation correction (c.853T-C) has been achieved by homologydirected repair (HDR) with ssODN harbouring wild-type sequence. In the second strategy, an enhanced version ofAGXTcDNAhas been inserted near the transcription start codon of the endogenous gene, constituting an almost universal correction strategy for PH1 mutations. Direct reprogramming of fibroblasts has been conducted by overexpression of hepatic transcription factors and in vitro culture in defined media. In vitro characterization of healthy induced hepatocytes (iHeps) has demonstrated hepatic function of the reprogrammed cells. PH1 patient fibroblasts and , , ,
000098333 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000098333 590__ $$a4.273$$b2019
000098333 591__ $$aBIOTECHNOLOGY & APPLIED MICROBIOLOGY$$b30 / 156 = 0.192$$c2019$$dQ1$$eT1
000098333 591__ $$aGENETICS & HEREDITY$$b38 / 177 = 0.215$$c2019$$dQ1$$eT1
000098333 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b40 / 138 = 0.29$$c2019$$dQ2$$eT1
000098333 592__ $$a1.648$$b2019
000098333 593__ $$aGenetics$$c2019$$dQ1
000098333 593__ $$aMolecular Medicine$$c2019$$dQ1
000098333 593__ $$aMolecular Biology$$c2019$$dQ2
000098333 655_4 $$ainfo:eu-repo/semantics/conferenceObject$$vinfo:eu-repo/semantics/publishedVersion
000098333 700__ $$aGarcia-Torralba, A.
000098333 700__ $$aMolinos-Vicente, A.
000098333 700__ $$aGarcia-Escudero, R.
000098333 700__ $$aPla-Palacin, I.
000098333 700__ $$0(orcid)0000-0002-8969-7726$$aBaptista, P.M.
000098333 700__ $$aSalido, E.
000098333 700__ $$aSegovia, J.C.
000098333 700__ $$aGarcia-Bravo, M.
000098333 773__ $$g30, 11 (2019), A144$$pHum. gene ther.$$tHUMAN GENE THERAPY$$x1043-0342
000098333 85641 $$uhttps://www.liebertpub.com/doi/pdf/10.1089/hum.2019.29095.abstracts$$zTexto completo de la revista
000098333 8564_ $$s41656$$uhttps://zaguan.unizar.es/record/98333/files/texto_completo.pdf$$yVersión publicada
000098333 8564_ $$s3536629$$uhttps://zaguan.unizar.es/record/98333/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000098333 909CO $$ooai:zaguan.unizar.es:98333$$particulos$$pdriver
000098333 951__ $$a2021-01-26-15:08:58
000098333 980__ $$aARTICLE