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Titolo:
A modified adenovirus can transfect cochlear hair cells in vivo without compromising cochlear function
Autore:
Luebke, AE; Steiger, JD; Hodges, BL; Amalfitano, A;
Indirizzi:
Univ Miami, Ear Inst M805, Dept Otolaryngol, Miami, FL 33101 USA Univ Miami Miami FL USA 33101 M805, Dept Otolaryngol, Miami, FL 33101 USA Univ Miami, Sch Med, Program Neurosci, Miami, FL 33101 USA Univ Miami Miami FL USA 33101 Med, Program Neurosci, Miami, FL 33101 USA Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27710 USA Duke Univ Durham NC USA 27710 Pediat, Div Med Genet, Durham, NC 27710 USA Duke Univ, Med Ctr, Dept Genet, Durham, NC 27710 USA Duke Univ Durham NC USA 27710 , Med Ctr, Dept Genet, Durham, NC 27710 USA
Titolo Testata:
GENE THERAPY
fascicolo: 10, volume: 8, anno: 2001,
pagine: 789 - 794
SICI:
0969-7128(200105)8:10<789:AMACTC>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
GENE-TRANSFER; NEUROTROPHIC FACTOR; INNER-EAR; THERAPY; VECTORS; MICE; E1; TRANSDUCTION; POLYMERASE; EXPRESSION;
Keywords:
cytomegalovirus promoter; LacZ reporter; replication-defective; cochlea; hair cell; distortion-product otoacoustic emissions;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Luebke, AE Univ Miami, Ear Inst M805, Dept Otolaryngol, POB 016960, Miami,FL 33101 USA Univ Miami POB 016960 Miami FL USA 33101 0, Miami, FL 33101 USA
Citazione:
A.E. Luebke et al., "A modified adenovirus can transfect cochlear hair cells in vivo without compromising cochlear function", GENE THER, 8(10), 2001, pp. 789-794

Abstract

The loss of cochlear hair cells, or the loss of their capacity to transduce acoustic signals, is believed to be the underlying mechanism in many forms of hearing loss. To develop viral vectors that allow for the introductionof genes directly into the cochleae of adult animals, replication-deficient (E1(-), E3(-)) and replication-defective (E1(-), E3(-), pol(-)) adenovirus vectors were used to transduce the bacterial beta -galactosidase gene into the hair cells of the guinea pig cochlea in vivo. Distortion product otoacoustic emissions, which monitor the functional status of outer hair cells,were measured throughout the viral infection periods to identify hair cellototoxicity. The results demonstrated that the use of the (E1(-), E3-) adenovirus vectors containing CMV-driven LacZ, compromised cochlear function when gradually introduced into scala tympani via an osmotic pump. However, when (E1(-), E3(-), pol(-)) adenoviral vectors containing CMV-driven LacZ were used to transduce cochlear hair cells, there was no loss of cochlear function over the frequency regions tested, and beta -galactosidase (beta -gal) was detected in over 80% of all hair cells. Development of a viral vectorthat infects cochlear hair cells without virus-induced ototoxic effects iscrucial for gene replacement strategies to treat certain forms of inherited deafness and for otoprotective strategies to prevent hair cell losses to treat progressive hearing disorders. Moreover, in vivo (E1(-), E3(-), pol(-)) adenovirus mediated gene-transfer techniques applied to adult guinea pigcochleae may be useful in testing several hypotheses concerning what rolesspecific genes play in normal cochlear function.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 22:37:19