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Intranuclear disposition of exogenous DNA in vivo: Silencing, methylation and fragmentation
Author(s) -
Ochiai Hiroshi,
Harashima Hideyoshi,
Kamiya Hiroyuki
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.01.017
Subject(s) - dna methylation , microbiology and biotechnology , methylation , dna , plasmid , naked dna , luciferase , biology , chemistry , gene expression , gene , biochemistry , transfection
The intranuclear disposition of exogenous DNA is highly important for the therapeutic effects of the administrated DNA. Naked luciferase‐plasmid DNA was delivered into mouse liver by a hydrodynamics‐based injection, and the amounts of intranuclear plasmid DNA, luciferase, and its mRNA were quantitated at various time points. Methylation of the promoter of the luciferase gene was also analyzed. Expression efficiency from one copy of the exogenous DNA dramatically decreased over time, and the DNA was methylated and degraded into fragments. Unexpectedly, methylation of the intact plasmid DNA was low and did not increase over time. Rather, the fragmented DNA was methylated more frequently than the intact plasmid. These results suggest that the CpG methylation and the degradation of exogenous DNA, and its ‘silencing’, occurred in parallel in the nucleus.