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Titolo:
Retargeting of adenoviral vectors to neurons using the H-c fragment of tetanus toxin
Autore:
Schneider, H; Groves, M; Muhle, C; Reynolds, PN; Knight, A; Themis, M; Carvajal, J; Scaravilli, F; Curiel, DT; Fairweather, NF; Coutelle, C;
Indirizzi:
Imperial Coll Sch Med, Div Biomed Sci, Mol Genet Sect, London SW7 2AZ, England Imperial Coll Sch Med London England SW7 2AZ ct, London SW7 2AZ, England Univ Coll London, Neurol Inst, Dept Neuropathol, London, England Univ CollLondon London England Inst, Dept Neuropathol, London, England Univ Alabama, Gene Therapy Program, Birmingham, AL USA Univ Alabama Birmingham AL USA Gene Therapy Program, Birmingham, AL USA Univ London Imperial Coll Sci Technol & Med, Dept Biochem, London, EnglandUniv London Imperial Coll Sci Technol & Med London England don, England
Titolo Testata:
GENE THERAPY
fascicolo: 18, volume: 7, anno: 2000,
pagine: 1584 - 1592
SICI:
0969-7128(200009)7:18<1584:ROAVTN>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
RETROGRADE AXONAL-TRANSPORT; CENTRAL-NERVOUS-SYSTEM; TARGETED GENE DELIVERY; RECOMBINANT ADENOVIRUS; GROWTH-FACTOR; PROTEINS; THERAPY; CELLS; DNA; EFFICIENCY;
Keywords:
tetanus toxin; adenovirus; retargeting; nervous system; gene transfer;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Coutelle, C Imperial Coll Sch Med, Div Biomed Sci, Mol Genet Sect, London SW7 2AZ, England Imperial Coll Sch Med London England SW7 2AZ W7 2AZ, England
Citazione:
H. Schneider et al., "Retargeting of adenoviral vectors to neurons using the H-c fragment of tetanus toxin", GENE THER, 7(18), 2000, pp. 1584-1592

Abstract

The H-C fragment of tetanus toxin (H-C) retains the specific nerve cell binding and transport properties of the holotoxin, but lacks any toxicity. Weare investigating the potential for utilising its neurotropism for targeted gene delivery to the central nervous system. Previously we reported the use of H-C-polylysine conjugates for selective gene transfer into neuronal cells in vitro. However, as attempts to apply these constructs in vivo were not successful, we have extended these studies to modification of the tropism of adenoviral vectors. Either H-C-polylysine conjugates or the Fab fragment of a neutralising anti-knob antibody covalently bound to H-C were attached to the virus. Infection of neuronal and nonneuronal cell lines with retargeted virus showed highly increased neuronal cell selectivity, but no significant enhancement of gene delivery into these cells. High concentrationsof free H-C blocked the infectivity of the retargeted vector efficiently. Intramuscular injection of retargeted virus into mouse tongues resulted in selective gene transfer to the neurons of the hypoglossal nucleus, where nopathological changes were observed As differentiated neurons do not undergo cell division, appropriate vectors carrying a thymidine kinase gene, which allows selective elimination of dividing cells, may be exploitable for the treatment of tumours of the central nervous system. The demonstrated suitability of the H-C fragment of tetanus toxin as targeting moiety for viral vectors also indicates a potential for gene therapy of inherited neurodegenerative diseases such as spinal muscular atrophy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 10:38:36