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_c13494 _d13494 |
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005 | 20210625062812.0 | ||
008 | 130622s2013 xxx||||| |||| 00| 0 eng d | ||
040 | _cH12O | ||
041 | _aeng | ||
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_aEnríquez de Salamanca Lorente, Rafael _9763 _eInstituto de Investigación i+12 |
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_aHelper-dependent adenoviral liver gene therapy protects against induced attacks and corrects protein folding stress in acute intermittent porphyria mice. _h[artículo] |
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_bHuman Molecular Genetics, _c2013 |
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300 | _a22(14):2929-40. | ||
500 | _aFormato Vancouver: Unzu C, Sampedro A, Mauleón I, González-Aparicio M, Enríquez de Salamanca R, Prieto J et al. Helper-dependent adenoviral liver gene therapy protects against induced attacks and corrects protein folding stress in acute intermittent porphyria mice. Hum Mol Genet. 2013 Jul 15;22(14):2929-40. | ||
501 | _aPMID: 23562909 | ||
504 | _aContiene 46 referencias | ||
520 | _aAcute intermittent porphyria (AIP) is a hepatic metabolic disease that results from haplo-insufficient activity of porphobilinogen deaminase (PBGD). The dominant clinical feature is acute intermittent attacks when hepatic heme synthesis is activated by endocrine or exogenous factors. Gene therapy vectors over-expressing PBGD protein in the liver offers potential as a cure for AIP. Here, we developed a helper-dependent adenovirus (HDA) encoding human PBGD (hPBGD) and assessed its therapeutic efficacy in a murine model of AIP. Intravenous or intrahepatic administration of HDA-hPBGD to AIP mice resulted in a sustained hepatic hPBGD expression in a dose-dependent manner. Intrahepatic administration conveyed full protection against induced porphyria attacks at a significantly lower viral dose than intravenous injection. Transgenic hPBGD accumulated only in the cytosol of hepatocytes as the endogenous protein. Characterization of PBGD-deficient mouse strains revealed that a strong PBGD deficiency causes the chronic disturbance of cytosolic and endoplasmic reticulum folding machineries. This disturbance was completely restored over time by the over-expression of hPBGD. HDA-hPBGD is a promising vector that protects against porphyria attacks and resolves the chronic folding stress associated with low levels of PBGD activity. | ||
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_9625 _aInstituto de Investigación imas12 |
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_uhttp://pc-h12o-es.m-hdoct.a17.csinet.es/pdf/pc/1/pc13494.pdf _ySolicitar documento |
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