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Herpes simplex virus-based vectors for gene delivery to the mammalian nervous system with reference to gene therapy of lysosomal disorders
Reference
CE09147
Principal Investigator / Supervisor
Professor Stacey Efstathiou
Co-Investigators /
Co-Supervisors
Professor Timothy Cox
,
Dr Stephen Inglis
Institution
University of Cambridge
Department
Pathology
Funding type
Research
Value (£)
334,673
Status
Completed
Type
Research Grant
Start date
01/09/1997
End date
01/09/2000
Duration
36 months
Abstract
Interest in HSV-based vectors for neuronal gene delivery stems from the natural ability of this virus to establish a life-long latent infection within neurones of both the peripheral and central nervous system. However, the cytolyic characteristics of HSV present potential risks involved in the use of viruses for practical or experimental purposes and attempts to achieve long-term gene expression in latently-infected tissues using HSV-based vectors have proved problematic. In order to address these key issues, the research outlined in this application seeks to (a) construct and characterise replication-defective HSV vector backbones carrying defects both in defined immediate early and essential late gene products; (b) characterise the capacity of the HSV latency associate transcript (LAT) promoter and other well studied promoter/regulatory elements to drive long-term gene expression in the mammalian nervous system. In order to assess the potential therapeutic benefit afforded by HSV-based vectors, a replication defective virus encoding the human arylsulphate A (ASA) gene, which is defective in the lysosomal storage disorder metachromatic leucodystrophy (MLD), will be constructed. The ASA gene will be placed under control of a functional LAT promoter/regulatory element and the therapeutic potential of this recombinant virus will be assessed in a gene knockout mouse model of MLD.
Summary
unavailable
Committee
Closed Committee - Genes & Developmental Biology (GDB)
Research Topics
X – not assigned to a current Research Topic
Research Priority
X – Research Priority information not available
Research Initiative
Cell Engineering - GDB Committee (CE) [1994-1996]
Funding Scheme
X – not Funded via a specific Funding Scheme
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