The integration profile of EIAV-based vectors.
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.
Hacker
Caroline V
CV
Oxford BioMedica UK Ltd., Medawar Centre, The Oxford Science Park, Oxford OX4 4GA, UK. c.hacker@oxfordbiomedica.co.uk
Vink
Conrad A
CA
Wardell
Theresa W
TW
Lee
Sheena
S
Treasure
Peter
P
Kingsman
Susan M
SM
Mitrophanous
Kyriacos A
KA
Miskin
James E
JE
D001482:Base Composition / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D002877:Chromosomes, Human / Q000235:genetics; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D004860:Infectious Anemia Virus, Equine / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics