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Titolo: Selective enhancement of gene transfer by steroid-mediated gene delivery
Autore: Rebuffat, A; Bernasconi, A; Ceppi, M; Wehrli, H; Verca, SB; Ibrahim, M; Frey, BM; Frey, FJ; Rusconi, S;
- Indirizzi:
- Univ Fribourg, UNIFR, Inst Biochem, CH-1700 Fribourg, Switzerland Univ Fribourg Fribourg Switzerland CH-1700 CH-1700 Fribourg, Switzerland Univ Bern, Inselspital, Div Nephrol, CH-3010 Bern, Switzerland Univ Bern Bern Switzerland CH-3010 iv Nephrol, CH-3010 Bern, Switzerland UNIFR, Inst Histol, CH-1700 Fribourg, Switzerland UNIFR Fribourg Switzerland CH-1700 Histol, CH-1700 Fribourg, Switzerland
- Titolo Testata:
- NATURE BIOTECHNOLOGY
fascicolo: 12,
volume: 19,
anno: 2001,
pagine: 1155 - 1161
- SICI:
- 1087-0156(200112)19:12<1155:SEOGTB>2.0.ZU;2-B
- Fonte:
- ISI
- Lingua:
- ENG
- Soggetto:
- ESTROGEN-RECEPTOR-BETA; GLUCOCORTICOID RECEPTOR; NUCLEAR IMPORT; PLASMID DNA; PROSTATE-CANCER; BREAST-CANCER; EXPRESSION; CELLS; EFFICIENT; PEPTIDE;
- Tipo documento:
- Article
- Natura:
- Periodico
- Settore Disciplinare:
- Agriculture,Biology & Environmental Sciences
- Life Sciences
- Citazioni:
- 43
- Recensione:
- Indirizzi per estratti:
- Indirizzo: Rusconi, S Univ Fribourg, UNIFR, Inst Biochem, CH-1700 Fribourg, Switzerland Univ Fribourg Fribourg Switzerland CH-1700 bourg, Switzerland
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- Citazione:
- A. Rebuffat et al., "Selective enhancement of gene transfer by steroid-mediated gene delivery", NAT BIOTECH, 19(12), 2001, pp. 1155-1161
Abstract
The incorporation of transgenes into the host cells' nuclei is problematicusing conventional nonviral gene delivery technologies. Here we describe astrategy, called steroid-mediated gene delivery (SMGD), which uses steroidreceptors as shuttles to facilitate the uptake of transfected DNA into thenucleus. We use glucocorticoid receptors (GRs) as a model system with which to test the principle of SMGD. To this end, we synthesized and tested several bifunctional steroid derivatives, finally focusing on a compound namedDR9NP, consisting of a dexamethasone backbone linked to a psoralen moiety using a nine-atom chemical spacer. DR9NP binds to the GR in either its freeor DNA-crosslinked form, inducing the translocation of the GR to the nucleus. The expression of transfected DR9NP-decorated reporter plasmids is enhanced in dividing cells: expression of steroid-decorated reporter plasmids depends on the presence of the GR, is independent of the transactivation potential of the GR, and correlates with enhanced nuclear accumulation of the transgene in GR-positive cells. The SMGD effect is also observed in cells naturally expressing GRs and is significantly increased in nondividing cell cultures. We propose that SMGD could be used as a platform for selective targeting of transgenes in nonviral somatic gene transfer.
ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 09:19:29