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Titolo:
Towards global and long-term neurological gene therapy: Unexpected transgene dependent, high-level, and widespread distribution of HSV-1 thymidine kinase throughout the CNS
Autore:
Zermansky, AJ; Bolognani, F; Stone, D; Cowsill, CM; Morrissey, G; Castro, MG; Lowenstein, PR;
Indirizzi:
Univ Manchester, Mol Med & Gene Therapy Unit, Manchester M13 9PT, Lancs, England Univ Manchester Manchester Lancs England M13 9PT M13 9PT, Lancs, England Gene Therapeut Res Inst, Los Angeles, CA 90048 USA Gene Therapeut Res Inst Los Angeles CA USA 90048 os Angeles, CA 90048 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 5, volume: 4, anno: 2001,
pagine: 490 - 498
SICI:
1525-0016(200111)4:5<490:TGALNG>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
CENTRAL-NERVOUS-SYSTEM; ADENOVIRAL VECTORS; BRAIN INFLAMMATION; WHITE-MATTER; EXPRESSION; NEURONS; EFFICIENT; CELLS;
Keywords:
adenovirus; brain; HSV1-TK; transgene specific;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Lowenstein, PR Univ Manchester, Mol Med & Gene Therapy Unit, Room 1-302 Stopford Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England Univ Manchester Room 1-302 Stopford Bldg,Oxford Rd Manchester Lancs England M13 9PT
Citazione:
A.J. Zermansky et al., "Towards global and long-term neurological gene therapy: Unexpected transgene dependent, high-level, and widespread distribution of HSV-1 thymidine kinase throughout the CNS", MOL THER, 4(5), 2001, pp. 490-498

Abstract

One of the challenges of neurological gene therapy for the treatment of chronic neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases, is achieving high levels, widespread distribution, and long-lived transgene expression in the brain. Here, following the intracerebral injectionof a recombinant adenovirus (RAd) encoding herpes simplex virus type 1 thymidine kinase (HSV1-TK), we detect very high levels of HSV1-TK immunoreactivity throughout the brain both ipsilaterally and contralaterally to the injection site, for up to 12 months following vector administration. This study concludes that long-term, high-level, and anatomically distributed HSV1-TK immunoreactivity can be obtained, and that this is most likely due to transgene-specific properties, because neither the distribution nor the longevity were observed for the transgene beta -galactosidase encoded by a co-injected vector. Thus, we demonstrate that transgene expression can be achieved over widespread areas of the rodent brain, even 12 months after a single injection of first-generation adenovirus vector.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 03:59:42