Combined injection of rAAV with mannitol enhances gene expression in the rat brain

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dc.citation.issue2
dc.citation.volume3
dc.contributor.authorMastakov M
dc.contributor.authorBaer K
dc.contributor.authorXu R
dc.contributor.authorFitzsimons H
dc.contributor.authorDuring M
dc.date.available2001-02
dc.date.issued2000-09-06
dc.description.abstractRecombinant 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, in addition to improvements in expression cassettes and viral titers, optimal injection 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 still excessively 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 significantly higher 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.
dc.description.publication-statusPublished
dc.format.extent225 - 232
dc.identifierhttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000167343800012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=c5bb3b2499afac691c2e3c1a83ef6fef
dc.identifier.citationMOLECULAR THERAPY, 2001, 3 (2), pp. 225 - 232
dc.identifier.doi10.1006/mthe.2001.0246
dc.identifier.elements-id445074
dc.identifier.harvestedMassey_Dark
dc.identifier.issn1525-0016
dc.publisherCell Press
dc.relation.isPartOfMOLECULAR THERAPY
dc.relation.urihttps://www.sciencedirect.com/science/article/pii/S1525001601902461?via%3Dihub
dc.rightsUnder a Creative Commons license
dc.subjectrAAV
dc.subjectmannitol
dc.subjectinjection parameters
dc.subjectCNS
dc.subjectgene therapy
dc.subject.anzsrc06 Biological Sciences
dc.subject.anzsrc10 Technology
dc.subject.anzsrc11 Medical and Health Sciences
dc.titleCombined injection of rAAV with mannitol enhances gene expression in the rat brain
dc.typeJournal article
pubs.notesNot known
pubs.organisational-group/Massey University
pubs.organisational-group/Massey University/College of Sciences
pubs.organisational-group/Massey University/College of Sciences/School of Natural Sciences
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