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Titolo:
HSV amplicon-mediated neurotrophin-3 expression protects murine spiral ganglion neurons from cisplatin-induced damage
Autore:
Chen, XW; Frisina, RD; Bowers, WJ; Frisina, DR; Federoff, HJ;
Indirizzi:
Univ Rochester, Sch Med & Dent, Ctr Aging & Dev Biol, Rochester, NY 14642 USA Univ Rochester Rochester NY USA 14642 & Dev Biol, Rochester, NY 14642 USA Univ Rochester, Sch Med & Dent, Div Otolaryngol, Rochester, NY 14642 USA Univ Rochester Rochester NY USA 14642 tolaryngol, Rochester, NY 14642 USA Univ Rochester, Sch Med & Dent, Dept Surg, Rochester, NY 14642 USA Univ Rochester Rochester NY USA 14642 Dept Surg, Rochester, NY 14642 USA Univ Rochester, Sch Med & Dent, Dept Neurobiol & Anat, Rochester, NY 14642USA Univ Rochester Rochester NY USA 14642 biol & Anat, Rochester, NY 14642USA Univ Rochester, Sch Med & Dent, Dept Biomed Engn, Rochester, NY 14642 USA Univ Rochester Rochester NY USA 14642 iomed Engn, Rochester, NY 14642 USA Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA Univ Rochester Rochester NY USA 14642 ept Neurol, Rochester, NY 14642 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 6, volume: 3, anno: 2001,
pagine: 958 - 963
SICI:
1525-0016(200106)3:6<958:HANEPM>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
REGULATED SECRETORY PATHWAY; DEVELOPING INNER-EAR; MESSENGER-RNAS; HEARING-LOSS; IN-VIVO; SENSORY NEURONS; TRKB RECEPTORS; GENE-TRANSFER; GUINEA-PIG; HAIR-CELLS;
Keywords:
growth factors; auditory nerve; gene therapy; deafness; amplicon;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Federoff, HJ Univ Rochester, Sch Med & Dent, Div Mol Med & Gene Therapy, Box 645,601 Elmwood Ave, Rochester, NY 14642 USA Univ Rochester Box 645,601 Elmwood Ave Rochester NY USA 14642
Citazione:
X.W. Chen et al., "HSV amplicon-mediated neurotrophin-3 expression protects murine spiral ganglion neurons from cisplatin-induced damage", MOL THER, 3(6), 2001, pp. 958-963

Abstract

Ototoxicity is a major dose-limiting side effect of cisplatin (DDP) administration due to its propensity to induce destruction of hair cells and neurons in the auditory system. Previous studies demonstrated that TrkC-expressing spiral ganglion neurons (SGN) are protected from the cytotoxic effects of DDP by localized delivery of the trophic factor neurotrophin-3 (NT-3). Successful in vivo implementation of such a therapy requires the developmentof an efficient gene delivery vehicle for expression of NT-3 within the cochlea. To this end, we constructed a herpes simplex virus (HSV) amplicon vector that expressed a c-Myc-tagged NT-3 chimera (HSVnt-3myc). Helper virus-free vector stocks were initially evaluated in vitro for their capacity to direct expression of NT-3 mRNA and protein. Transduction of cultured murinecochlear explants with HSVnt-3myc resulted in production of NT-3 mRNA and protein up to 3 ng/ml as measured over a 48-h period in culture supernatants. To determine whether NT-3 overexpression could abrogate DDP toxicity, cochlear explants were transduced with HSVnt-3myc or a murine intestinal alkaline phosphatase-expressing control vector, HSVmiap, and then exposed to cisplatin. HSVnt-3myc-transduced cochlear explants harbored significantly greater numbers of surviving SGNs than those infected with control virus. These data demonstrate that amplicon-mediated NT-3 transduction can attenuate the ototoxic action of DDP on organotypic culture. The potency of NT-3 in protecting spiral ganglion neurons from degeneration suggests that in vivo neurotrophin-based gene therapy may be useful for the prevention and/or treatment of hearing disorders.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/02/20 alle ore 21:39:08