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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
2009-11-2
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pubmed:abstractText |
Correction of a defective gene is a promising approach for both basic research and clinical gene therapy. However, the absence of site-specific targeting and the low efficiency of homologous recombination in human cells present barriers to successful gene targeting. In an effort to overcome these barriers, we utilized triplex-forming oligonucleotides (TFOs) conjugated to a DNA interstrand crosslinking (ICL) agent, psoralen (pTFO-ICLs), to improve the gene targeting efficiency at a specific site in DNA. Gene targeting events were monitored by the correction of a deletion on a recipient plasmid with the homologous sequence from a donor plasmid in human cells. The mechanism underlying this event is stimulation of homologous recombination by the pTFO-ICL. We found that pTFO-ICLs are efficient in inducing targeted gene conversion (GC) events in human cells. The deletion size in the recipient plasmid influenced both the recombination frequency and spectrum of recombinants; i.e. plasmids with smaller deletions had a higher frequency and proportion of GC events. The polarity of the pTFO-ICL also had a prominent effect on recombination. Our results suggest that pTFO-ICL induced intermolecular recombination provides an efficient method for targeted gene correction in mammalian cells.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-10064704,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-10206960,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-10629056,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-10882712,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-10900269,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-11106642,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-11459982,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-11516927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-11812847,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-11884621,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-11905724,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-12461167,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-1303270,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-15375217,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-15891767,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-16569514,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-16731047,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-17669695,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-18006494,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-18628293,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-18787700,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-18996898,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-19468048,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-2003222,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-2411210,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-2555716,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-2708342,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-2943972,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-3007275,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-3161076,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-3293213,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-3523485,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-3534882,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-4577788,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-6281782,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-6297747,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-6380756,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-6752694,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-7026973,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-7528895,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-7548210,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-8114699,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-8159731,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-8284208,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-8420966,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-8533154,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-8596475,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-8643590,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-8943337,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-8972207,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19726585-9683673
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1362-4962
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
37
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6378-88
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pubmed:dateRevised |
2010-9-27
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pubmed:meshHeading |
pubmed-meshheading:19726585-Cross-Linking Reagents,
pubmed-meshheading:19726585-DNA,
pubmed-meshheading:19726585-Ficusin,
pubmed-meshheading:19726585-Gene Conversion,
pubmed-meshheading:19726585-Gene Deletion,
pubmed-meshheading:19726585-HeLa Cells,
pubmed-meshheading:19726585-Humans,
pubmed-meshheading:19726585-Oligonucleotides,
pubmed-meshheading:19726585-Polymerase Chain Reaction,
pubmed-meshheading:19726585-Recombination, Genetic
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pubmed:year |
2009
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pubmed:articleTitle |
Targeted gene conversion induced by triplex-directed psoralen interstrand crosslinks in mammalian cells.
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pubmed:affiliation |
Department of Carcinogenesis, University of Texas MD Anderson Cancer Center, Science Park-Research Division, Smithville, Texas, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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