Hepatitis B Virus-Based Vectors Allow the Elimination of Viral Gene Expression and the Insertion of Foreign Promoters
| العنوان: | Hepatitis B Virus-Based Vectors Allow the Elimination of Viral Gene Expression and the Insertion of Foreign Promoters |
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| المؤلفون: | Andreas Untergasser, Ulrike Protzer |
| المصدر: | Human Gene Therapy. 15:203-210 |
| بيانات النشر: | Mary Ann Liebert Inc, 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Gene Expression Regulation, Viral, Hepatitis B virus, Genetic Vectors, Biology, medicine.disease_cause, Hepatitis B virus PRE beta, Virus, Transduction, Genetic, Gene expression, Genetics, medicine, Humans, Transgenes, Vector (molecular biology), ORFS, Promoter Regions, Genetic, Molecular Biology, Gene knockout, Recombination, Genetic, virus diseases, Genetic Therapy, biology.organism_classification, Virology, digestive system diseases, Hepadnaviridae, Hepatocytes, Molecular Medicine, Helper Viruses, Plasmids |
| الوصف: | It has recently been shown that hepatitis B virus (HBV)-based vectors are suitable for a hepatocyte specific gene transfer. As candidate vectors for gene therapy, however, they should no longer express any viral gene products. In addition, the insertion of promoters that do not originate from HBV is needed to allow a variation of the level of gene expression. Furthermore, production of high-titer stocks is required. To eliminate viral gene expression, we knocked out all HBV open reading frames (ORFs) in the transfer construct used to express recombinant HBV RNA. To minimize the chance of homologous recombination, we generated an improved helper construct. With these constructs, recombinant viruses containing single or combined knockouts of the viral ORFs were produced at titers equal to wild-type HBV produced in parallel. We identified a site in the HBV genome that allows insertion of foreign promoter elements without interfering with maturation of infectious HBV particles. Successful gene transfer was demonstrated on infection of primary human hepatocytes using recombinant HBV in which all viral ORFs were knocked out and a foreign promoter controlled transgene expression. These improvements represent a major step toward the development of HBV vectors as candidates for human gene therapy. |
| تدمد: | 1557-7422 1043-0342 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8b70a09a3cf9d1dd37696e904ecc03b6Test https://doi.org/10.1089/104303404772680001Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....8b70a09a3cf9d1dd37696e904ecc03b6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15577422 10430342 |
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