期刊
MOLECULAR THERAPY
卷 15, 期 12, 页码 2132-2139出版社
CELL PRESS
DOI: 10.1038/sj.mt.6300275
关键词
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资金
- NHLBI NIH HHS [P01 HL071643, R01 HL059956-09, P01 HL071643-040005, HL59956, HL71643, R01 HL059956] Funding Source: Medline
Our aim is to characterize the poorly understood mechanisms that influence episomal transgene expression within the nucleus. We found that plasmid DNA micro-injected directly into a nucleus moves into a speckled pattern and occupies less nuclear volume than bovine serum albumin (BSA) or other inert molecules after 4 hours. In addition, plasmids that contain eukaryotic regulatory sequences and actively transcribe transgenes condense into a few select areas of the nucleoplasm and occupy less nuclear volume than bacterial vectors. This suggests that episomal DNA moves in a sequence and transcription-dependent manner. We have also found that plasmids traffic to specific subnuclear domains depending on their sequence. Our experiments show that plasmids with polymerase II regulatory elements will target to nuclear spliceosome regions, while plasmids with the polymerase I promoter often traffic into nucleoli. Further elucidation of intranuclear plasmid trafficking behavior may lead to a better understanding of gene expression, and thereby help to improve basic laboratory techniques and clinical gene therapies.
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