The integration profile of EIAV-based vectors

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Abstract

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. © 2006 The American Society of Gene Therapy.

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Hacker, C. V., Vink, C. A., Wardell, T. W., Lee, S., Treasure, P., Kingsman, S. M., … Miskin, J. E. (2006). The integration profile of EIAV-based vectors. Molecular Therapy, 14(4), 536–545. https://doi.org/10.1016/j.ymthe.2006.06.006

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