Title: Distinct genomic integration of MLV and SIV vectors in primate hematopoietic stem and progenitor cells
Authors: Hematti, Peiman ×
Hong, Bum-Kee
Ferguson, Cole
Adler, Rima
Hanawa, Hideki
Sellers, Stephanie
Holt, Ingeborg E
Eckfeldt, Craig E
Sharma, Yugal
Schmidt, Manfred
von Kalle, Christof
Persons, Derek A
Billings, Eric M
Verfaillie, Catherine
Nienhuis, Arthur W
Wolfsberg, Tyra G
Dunbar, Cynthia E
Calmels, Boris #
Issue Date: Dec-2004
Publisher: Public Library of Science
Series Title: PLoS Biology vol:2 issue:12 pages:2183-2190
Abstract: Murine leukemia virus (MLV)-derived vectors are widely used for hematopoietic stem cell (HSC) gene transfer, but lentiviral vectors such as the simian immunodeficiency virus (SIV) may allow higher efficiency transfer and better expression. Recent studies in cell lines have challenged the notion that retroviruses and retroviral vectors integrate randomly into their host genome. Medical applications using these vectors are aimed at HSCs, and thus large-scale comprehensive analysis of MLV and SIV integration in long-term repopulating HSCs is crucial to help develop improved integrating vectors. We studied integration sites in HSCs of rhesus monkeys that had been transplanted 6 mo to 6 y prior with MLV- or SIV-transduced CD34(+)cells. Unique MLV (491) and SIV (501) insertions were compared to a set of in silico-generated random integration sites. While MLV integrants were located predominantly around transcription start sites, SIV integrants strongly favored transcription units and gene-dense regions of the genome. These integration patterns suggest different mechanisms for integration as well as distinct safety implications for MLV versus SIV vectors.
ISSN: 1545-7885
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Interdepartemental Stem Cell Institute (-)
× corresponding author
# (joint) last author

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