PMID- 20372108
OWN - NLM
STAT- MEDLINE
DCOM- 20101005
LR  - 20211020
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 18
IP  - 6
DP  - 2010 Jun
TI  - Comparative analysis of transposable element vector systems in human cells.
PG  - 1200-9
LID - 10.1038/mt.2010.47 [doi]
AB  - Transposon-based gene vectors have become indispensable tools in vertebrate 
      genetics for applications ranging from insertional mutagenesis and transgenesis 
      in model species to gene therapy in humans. The transposon toolkit is expanding, 
      but a careful, side-by-side characterization of the diverse transposon systems 
      has been lacking. Here we compared the Sleeping Beauty (SB), piggyBac (PB), and 
      Tol2 transposons with respect to overall activity, overproduction inhibition 
      (OPI), target site selection, transgene copy number as well as long-term 
      expression in human cells. SB was the most efficient system under conditions 
      where the availability of the transposon DNA is limiting the transposition 
      reaction including hard-to-transfect hematopoietic stem/progenitor cells (HSCs), 
      and the most sensitive to OPI, underpinning the need for careful optimization of 
      the transposon components. SB and PB were about equally active, and both more 
      efficient than Tol2, under nonrestrictive conditions. All three systems provided 
      long-term transgene expression in human cells with minimal signs of silencing. 
      Indeed, mapping of Tol2 insertion sites revealed significant underrepresentation 
      within chromosomal regions with H3K27me3 histone marks typically associated with 
      transcriptionally repressed heterochromatin. SB, Tol2, and PB constitute 
      complementary research tools for gene transfer in mammalian cells with important 
      implications for fundamental and translational research.
FAU - Grabundzija, Ivana
AU  - Grabundzija I
AD  - Max Delbruck Center for Molecular Medicine, Berlin, Germany.
FAU - Irgang, Markus
AU  - Irgang M
FAU - Mates, Lajos
AU  - Mates L
FAU - Belay, Eyayu
AU  - Belay E
FAU - Matrai, Janka
AU  - Matrai J
FAU - Gogol-Doring, Andreas
AU  - Gogol-Doring A
FAU - Kawakami, Koichi
AU  - Kawakami K
FAU - Chen, Wei
AU  - Chen W
FAU - Ruiz, Patricia
AU  - Ruiz P
FAU - Chuah, Marinee K L
AU  - Chuah MK
FAU - VandenDriessche, Thierry
AU  - VandenDriessche T
FAU - Izsvak, Zsuzsanna
AU  - Izsvak Z
FAU - Ivics, Zoltan
AU  - Ivics Z
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100406
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (DNA Transposable Elements)
SB  - IM
MH  - *DNA Transposable Elements
MH  - *Genetic Vectors
MH  - HeLa Cells
MH  - Humans
MH  - Transgenes
PMC - PMC2889740
EDAT- 2010/04/08 06:00
MHDA- 2010/10/06 06:00
PMCR- 2011/06/01
CRDT- 2010/04/08 06:00
PHST- 2010/04/08 06:00 [entrez]
PHST- 2010/04/08 06:00 [pubmed]
PHST- 2010/10/06 06:00 [medline]
PHST- 2011/06/01 00:00 [pmc-release]
AID - S1525-0016(16)31059-0 [pii]
AID - 10.1038/mt.2010.47 [doi]
PST - ppublish
SO  - Mol Ther. 2010 Jun;18(6):1200-9. doi: 10.1038/mt.2010.47. Epub 2010 Apr 6.