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Titolo:
Combined injection of rAAV with mannitol enhances gene expression in the rat brain
Autore:
Mastakov, MY; Baer, K; Xu, R; Fitzsimons, H; During, MJ;
Indirizzi:
Thomas Jefferson Univ, Jefferson Med Coll, Dept Neurosurg, CNS Gene Therapy Ctr, Philadelphia, PA 19107 USA Thomas Jefferson Univ Philadelphia PA USA 19107 hiladelphia, PA 19107 USA Univ Auckland, Fac Med & Hlth Sci, Div Mol Med, Funct Genom & Translat Neurosci Lab, Auckland 1, New Zealand Univ Auckland Auckland New Zealand 1 urosci Lab, Auckland 1, New Zealand
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 2, volume: 3, anno: 2001,
pagine: 225 - 232
SICI:
1525-0016(200102)3:2<225:CIORWM>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECOMBINANT ADENOASSOCIATED VIRUS; CENTRAL-NERVOUS-SYSTEM; HEPARAN-SULFATE PROTEOGLYCAN; IN-VIVO EXPRESSION; TYROSINE-HYDROXYLASE; BARRIER DISRUPTION; VIRAL VECTORS; AAV VECTOR; TRANSGENE EXPRESSION; PARKINSONS-DISEASE;
Keywords:
rAAV; mannitol; injection parameters; CNS; gene therapy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: During, MJ Thomas Jefferson Univ, Jefferson Med Coll, Dept Neurosurg, CNS Gene Therapy Ctr, Philadelphia, PA 19107 USA Thomas Jefferson Univ Philadelphia PA USA 19107 , PA 19107 USA
Citazione:
M.Y. Mastakov et al., "Combined injection of rAAV with mannitol enhances gene expression in the rat brain", MOL THER, 3(2), 2001, pp. 225-232

Abstract

Recombinant adeno-associated viruses (rAAV) are highly efficient vectors for gene transfer into the central nervous system (CNS). However, a major hurdle for gene delivery to the mammalian brain is to achieve high-level transduction in target cells beyond the immediate injection site. Therefore, inaddition to improvements in expression cassettes and viral titers, optimalinjection parameters need to be defined. Here, we show that previous studies of somatic cell gene transfer to the mammalian brain have used suboptimal injection parameters, with even the lowest reported perfusion rates stillexcessively fast. Moreover, we evaluated the effect of local administration of mannitol to further enhance transgene expression and vector spread. Ultraslow microperfusion of rAAV, i.e., <33 nl/min, resulted in significantlyhigher gene expression and less injury of surrounding tissue than the previously reported rates of 100 nl/min or faster. Co-infusion of mannitol facilitated gene transfer to neurons, increasing both the total number and the distribution of transduced cells by 200-300%. Gene transfer studies in the CNS using rAAV should use very slow infusion rates and combined injection with mannitol to maximize transduction efficiency and spread.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 06:45:12