A Fourth Generation Lentiviral Vector: Simplifying Genomic Gymnastics
| العنوان: | A Fourth Generation Lentiviral Vector: Simplifying Genomic Gymnastics |
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| المؤلفون: | Ben Berkhout |
| المساهمون: | AII - Infectious diseases, Medical Microbiology and Infection Prevention, AII - Amsterdam institute for Infection and Immunity |
| المصدر: | Molecular therapy, 25(8), 1741-1743. Nature Publishing Group Molecular Therapy |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Gymnastics, HIV-1 remobilization, Computer science, Genetic enhancement, Transgene, Genetic Vectors, Gene transfer, Computational biology, Genome, Viral vector, splicing, 03 medical and health sciences, HIV-1 packaging, Transduction, Genetic, hemophilia, Drug Discovery, Genetics, Fourth generation, Vector (molecular biology), Stable gene, Molecular Biology, Pharmacology, business.industry, Lentivirus, viral vector, Genomics, reverse transcription, gene therapy, Biotechnology, 030104 developmental biology, Molecular Medicine, Original Article, business |
| الوصف: | Lentiviral vector genomic RNA requires sequences that partially overlap wild-type HIV-1 gag and env genes for packaging into vector particles. These HIV-1 packaging sequences constitute 19.6% of the wild-type HIV-1 genome and contain functional cis elements that potentially compromise clinical safety. Here, we describe the development of a novel lentiviral vector (LTR1) with a unique genomic structure designed to prevent transfer of HIV-1 packaging sequences to patient cells, thus reducing the total HIV-1 content to just 4.8% of the wild-type genome. This has been achieved by reconfiguring the vector to mediate reverse-transcription with a single strand transfer, instead of the usual two, and in which HIV-1 packaging sequences are not copied. We show that LTR1 vectors offer improved safety in their resistance to remobilization in HIV-1 particles and reduced frequency of splicing into human genes. Following intravenous luciferase vector administration to neonatal mice, LTR1 sustained a higher level of liver transgene expression than an equivalent dose of a standard lentivirus. LTR1 vectors produce reverse-transcription products earlier and start to express transgenes significantly quicker than standard lentiviruses after transduction. Finally, we show that LTR1 is an effective lentiviral gene therapy vector as demonstrated by correction of a mouse hemophilia B model. Counsell and colleagues have developed a novel lentiviral vector, LTR1, designed to minimize the incorporation of HIV-1 sequences during transduction. Their data show that LTR1 potentially offers improved safety in gene therapy, while demonstrating robust gene therapy efficacy in correcting a mouse model of hemophilia B. |
| اللغة: | English |
| تدمد: | 1525-0016 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2a1a387d025d2fff4e846da5df11aab8Test https://pure.amc.nl/en/publications/a-fourth-generation-lentiviral-vector-simplifying-genomic-gymnasticsTest(e1644c70-e92c-4435-98ec-7aae7091e343).html |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2a1a387d025d2fff4e846da5df11aab8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15250016 |
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