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Titolo:
Neurotensin-SPDP-poly-L-lysine conjugate: a nonviral vector for targeted gene delivery to neural cells
Autore:
Martinez-Fong, D; Navarro-Quiroga, I; Ochoa, I; Alvarez-Maya, I; Meraz, MA; Luna, J; Arias-Montano, JA;
Indirizzi:
Insteurociencias,l, Ctr Invest & Estudios Avanzados, Dept Fisiol Biofis & N Inst Politecn Nacl Mexico City DF Mexico 07000 os, Dept Fisiol Biofis & N Instnariotecn Nacl, Ctr Invest & Estudios Avanzados, Programa Multidiscipli Inst Politecn Nacl Mexico City DF Mexico 07000 os, Programa Multidiscipli Insticolitecn Nacl, Ctr Invest & Estudios Avanzados, Dept Biol Celular, Mex Inst Politecn Nacl Mexico City DF Mexico 07000 os, Dept Biol Celular, Mex
Titolo Testata:
MOLECULAR BRAIN RESEARCH
fascicolo: 2, volume: 69, anno: 1999,
pagine: 249 - 262
SICI:
0169-328X(19990608)69:2<249:NCANVF>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
RETROGRADE AXONAL-TRANSPORT; NIGROSTRIATAL DOPAMINERGIC-NEURONS; BIOLOGICAL-ACTIVITY; BINDING-PROPERTIES; HEPATOMA-CELLS; RAT STRIATUM; MOUSE-BRAIN; RECEPTOR; EXPRESSION; PROTEIN;
Keywords:
neurotensin receptor; receptor-mediated endocytosis; gene transfer; gene therapy; transgenic animal;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Martinez-Fong, D Insteurociencias,l, Ctr Invest & Estudios Avanzados, DeptFisiol Biofis & N Inst Politecn Nacl Apartado 14-740 Mexico City DF Mexico07000
Citazione:
D. Martinez-Fong et al., "Neurotensin-SPDP-poly-L-lysine conjugate: a nonviral vector for targeted gene delivery to neural cells", MOL BRAIN R, 69(2), 1999, pp. 249-262

Abstract

We report herein the synthesis of a novel DNA delivery system and in vitroevidence of its ability to transfect cell lines by binding to the high-affinity neurotensin receptor and subsequent internalization of ligand-receptor complexes. The targeting vehicle consisted of neurotensin crosslinked with poly-L-lysine via N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP). The SPDP-derivatives with either neurotensin or poly-L-lysine were purified by gel filtration. The conjugate resulting of the reaction of neurotensin-SPDP with HS-SPDP-poly-L-lysine was purified through Biogel A 1.5. The neurotensin-SPDP-poly-L-lysine conjugate was able to bind plasmidic DNAs (pSV2cat and pGreen Lantern-1) at optimal molar ratios of 1:5 and 1:6 (DNA: conjugate), respectively. The conjugate internalized those plasmids in the cell lines (N1E-115 and HT-29) bearing the high-affinity neurotensin receptor. Expression of the plasmid products, chloramphenicol acetyltransferase and green fluorescent protein, was observed in such cell lines. Both internalization and expression of the plasmids transferred by the neurotensin-SPDP-poly-L-lysine conjugate were prevented by neurotensin (1 mu M) and SR-48692 (100nM), a specific antagonist of the high-affinity neurotensin receptor. The neurotensin-SPDP-poly-L-lysine conjugate was unable to transfect cell lineslacking the neurotensin receptor (COS-7 and L-929). In rat brain, the high-affinity neurotensin receptor is expressed by specific neurons such as those of the nigrostriatal and mesolimbic dopaminergic systems. Therefore, theneurotensin-SPDP-poly-L-lysine conjugate could be a useful tool for gene delivery to those neuronal systems. (C) 1999 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 13:19:07