The integration profile of EIAV-based vectors

Mol Ther. 2006 Oct;14(4):536-45. doi: 10.1016/j.ymthe.2006.06.006.

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.

MeSH terms

  • Base Composition / genetics
  • Base Sequence
  • Cell Line
  • Chromosomes, Human / genetics
  • Gene Expression
  • Genetic Vectors / genetics*
  • Genome, Human / genetics
  • Humans
  • Infectious Anemia Virus, Equine / genetics*
  • Transcription, Genetic / genetics