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Titolo:
A regulated, NF kappa B-assisted import of plasmid DNA into mammalian cellnuclei
Autore:
Mesika, A; Grigoreva, I; Zohar, M; Reich, Z;
Indirizzi:
Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel Weizmann Inst Sci Rehovot Israel IL-76100 Chem, IL-76100 Rehovot, Israel Biotechnol Gen, Div Res, IL-76100 Rehovot, Israel Biotechnol Gen RehovotIsrael IL-76100 Div Res, IL-76100 Rehovot, Israel
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 5, volume: 3, anno: 2001,
parte:, 1
pagine: 653 - 657
SICI:
1525-0016(200105)3:5<653:ARNKBI>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
GENE-TRANSFER; NUCLEOCYTOPLASMIC TRANSPORT; TRANSCRIPTIONAL ACTIVATION; SUPERCOILED DNA; DELIVERY; THERAPY; SYSTEM; TRANSLOCATION; DEPENDENCE; CHEMISTRY;
Keywords:
synthetic gene therapy; nuclear pore complex; nuclear localization signal; nuclear factor kappa B; kappa B sites; tumor necrosis factor-alpha;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Reich, Z Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel Weizmann Inst Sci Rehovot Israel IL-76100 76100 Rehovot, Israel
Citazione:
A. Mesika et al., "A regulated, NF kappa B-assisted import of plasmid DNA into mammalian cellnuclei", MOL THER, 3(5), 2001, pp. 653-657

Abstract

The success of synthetic DNA delivery systems in human gene therapy will be enhanced by increasing transfection efficiencies and by providing tightercontrol over targeting of the DNA into the nucleus. Here, we used DNA vectors that contain repetitive binding sites for the inducible transcription factor NF kappaB, which is transported into the nucleus by the nuclear import machinery. Nuclear entry of the modified vectors was augmented 12-fold and was associated with corresponding increase in gene expression. Depending on their position, the binding sites could also function as transcriptionalenhancers, increasing gene expression levels up to an additional 19-fold. Notably, nuclear targeting of the DNA and transgene transcription could both be regulated by exogenous stimulators which modulate the intracellular distribution of NF kappaB. The approach provides a framework for the controlled targeting of constitutive or transcriptionally regulated synthetic vectors into mammalian cell nuclei.

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Documento generato il 19/02/20 alle ore 17:48:16