Effective treatment of familial hypercholesterolaemia in the mouse model using adenovirus–mediated transfer of the VLDL receptor gene
| Autor: | M Donahee, J F Strauss rd, James M. Wilson, Karin Jooss, Karen F. Kozarsky |
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| Rok vydání: | 1996 |
| Předmět: |
medicine.medical_specialty
Very low-density lipoprotein LRP1B Transgene Cytomegalovirus VLDL receptor Vaccinia virus Biology Hyperlipoproteinemia Type II Mice chemistry.chemical_compound Internal medicine Genetics medicine Animals Humans Promoter Regions Genetic Receptor Recombination Genetic Adenoviruses Human Gene Transfer Techniques DNA Genetic Therapy Mice Mutant Strains Blotting Southern Cholesterol Endocrinology Liver Receptors LDL chemistry Low-density lipoprotein LDL receptor lipids (amino acids peptides and proteins) Ectopic expression T-Lymphocytes Cytotoxic |
| Zdroj: | Nature Genetics. 13:54-62 |
| ISSN: | 1546-1718 1061-4036 |
| Popis: | Liver directed gene transfer with adenoviral vectors is being considered for the treatment of several metabolic diseases, including familial hypercholesterolaemia (FH). Gene replacement therapy of human low density lipoprotein (LDL) receptor gene into the murine model of FH transiently corrected the dyslipidaemia; however, humoral and cellular immune responses to LDL receptor developed--possibly contributing to the associated hepatitis and extinguishing of transgene expression. We evaluated an alternative strategy of ectopic expression in the liver of the very low density lipoprotein (VLDL) receptor, which is homologous to the LDL receptor but has a different pattern of expression. Infusion of recombinant adenoviruses containing the VLDL receptor gene corrected the dsylipidaemia in the FH mouse and circumvented immune responses to the transgene leading to a more prolonged metabolic correction. |
| Databáze: | OpenAIRE |
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