Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Transgene expression in the brain stem effected by intramuscular injectionof polyethylenimine/DNA complexes
Autore:
Wang, S; Ma, N; Gao, SJ; Yu, H; Leong, KW;
Indirizzi:
Natl Univ Singapore, Inst Mat Res & Engn, Biomat Tissue Engn Program, Singapore 117602, Singapore Natl Univ Singapore Singapore Singapore 117602 ngapore 117602, Singapore Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21205 USA Johns Hopkins Univ Baltimore MD USA 21205 d Engn, Baltimore, MD 21205 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 5, volume: 3, anno: 2001,
parte:, 1
pagine: 658 - 664
SICI:
1525-0016(200105)3:5<658:TEITBS>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
CENTRAL-NERVOUS-SYSTEM; GENE DELIVERY; IN-VIVO; MOTOR-NEURONS; SPINAL-CORD; VECTOR; TRANSFECTION; TRANSPORT; VIRUS; ADENOVIRUSES;
Keywords:
gene transfer; polyethylenimine; endocytosis; retrograde axonal transport; hypoglossal system; motor neuron diseases;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Wang, S Natl Univ Singapore, Inst Mat Res & Engn, Biomat Tissue Engn Program, 3 Res Link, Singapore 117602, Singapore Natl Univ Singapore 3 Res Link Singapore Singapore 117602 ngapore
Citazione:
S. Wang et al., "Transgene expression in the brain stem effected by intramuscular injectionof polyethylenimine/DNA complexes", MOL THER, 3(5), 2001, pp. 658-664

Abstract

Gene delivery into the CNS without tissue destruction is challenging. As neurons are capable of taking up exogenous particulates from the muscles that they innervate, we investigated the feasibility of achieving gene transfer in CNS neurons by peripheral intramuscular injection of plasmid DNA complexed with the cationic polymer polyethylenimine (PEI) in the rat hypoglossal system. Using the luciferase reporter gene driven by a Rous sarcoma viruspromoter, transgene expression of up to 4 x 10(6) RLU per brain stem at 20mug of plasmid DNA was achieved after tongue injection. Using lacZ as a reporter gene, transgene expression in the brain stem was detected in hypoglossal motor neurons, a group of neurons that innervate tongue muscles. The plasmid DNA was detected by PCR analysis in the brain-stem samples, demonstrating that the PEI/DNA complexes had migrated by retrograde axonal transport to neuronal cell bodies in the brain stem after being internalized by nerve terminals in the tongue muscle. Using a therapeutic bcl-2 gene driven bya cytomegalovirus promoter and Western blotting, transgene expression was detectable in the brain stem as early as 18 h after tongue injection and lasted for at least 2 weeks. Two lipid transfection agents, GenePORTER and TransFast, mediated a weak gene expression in the hypoglossal system, but nottwo polymers, poly-L-lysine and chitosan. The nonviral neuronal gene delivery method established in this study bypasses the blood-brain barrier and suggests a possible therapeutic strategy for noninvasive CNS 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 07:15:20