
pmid: 16950499
Lentiviral vectors based on equine infectious anemia virus (EIAV) stably integrate into dividing and nondividing cells such as neurons, conferring long-term expression of their transgene. The integration profile of an EIAV vector was analyzed in dividing HEK293T cells, alongside an HIV-1 vector as a control, and compared to a random dataset generated in silico. A multivariate regression model was generated and the influence of the following parameters on integration site selection determined: (a) within/not within a gene, (b) GC content within 20 kb, (c) within 10 kb of a CpG island, (d) gene density within a 2-Mb window, and (e) chromosome number. The majority of the EIAV integration sites (68%; n = 458) and HIV-1 integration sites (72%; n = 162) were within a gene, and both vectors favored AT-rich regions. Sites within genes were examined using a second model to determine the influence of the gene-specific parameters, gene region, and transcriptional activity. Both EIAV and HIV-1 vectors preferentially integrated within active genes. Unlike the gammaretrovirus MLV, EIAV and HIV-1 vectors do not integrate preferentially into the promoter region or the 5' end of the transcription unit.
Pharmacology, Base Composition, Base Sequence, Transcription, Genetic, Genome, Human, Genetic Vectors, Gene Expression, Cell Line, Drug Discovery, Genetics, Molecular Medicine, Chromosomes, Human, Humans, Molecular Biology, Infectious Anemia Virus, Equine
Pharmacology, Base Composition, Base Sequence, Transcription, Genetic, Genome, Human, Genetic Vectors, Gene Expression, Cell Line, Drug Discovery, Genetics, Molecular Medicine, Chromosomes, Human, Humans, Molecular Biology, Infectious Anemia Virus, Equine
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