Research article summary (published 30 Jan 2003):

Novel Semliki Forest virus vectors with reduced cytotoxicity and temperature sensitivity for long-term enhancement of transgene expression.

Full Abstract

Alphaviral vectors inhibit host cell protein synthesis and are cytotoxic. To overcome these limitations, we modified the nonstructural protein-2 (nsP2) gene in the Semliki Forest virus (SFV) vector, pSFV1. Packaging of SFV replicons with two point mutations in nsP2 resulted in high-titer recombinant SFV(PD) particles. SFV(PD) led to more efficient host cell protein synthesis, exhibited reduced cytotoxicity and improved cell survival, and allowed greater and prolonged transgene expression than the original vector, SFV. In dissociated hippocampal neurons and organotypic rat hippocampal slices, SFV(PD) infection preserved neuronal morphology and synaptic function more efficiently than SFV. Combination of the two point mutations with a replication-persistent mutation in nsP2 resulted in a highly temperature-sensitive vector, SFV(PD713P), which efficiently transduced neurons in hippocampal slice cultures. At 31 degrees C, SFV(PD713P) allowed continuous transgene expression in BHK cells, at amounts comparable to SFV(PD). These new SFV mutants are expected to substantially broaden the application of alphaviral vectors in neurons and other mammalian cells.

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Author information

Author/s: Lundstrom, Kenneth (K); Abenavoli, Alessandra (A); Malgaroli, Antonio (A); Ehrengruber, Markus U (MU);

Affiliation: Regulon Inc., Biopole Epalinges, Les Croisettes 22, CH-1066 Epalinges, Switzerland. Kenneth.Lundstrom(-atsign-)mepnet.org

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther), published in United States. (Language: eng)

Reference: 2003-Feb; vol 7 (issue 2) : pp 202-9

Dates: Created 2003/02/24; Completed 2003/09/11; Revised 2006/11/15;

PMID: 12597908, status: MEDLINE (last retrieval date: 11/6/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals CHO Cells Cell Line Cell Survival Cricetinae Electrophoresis, Polyacrylamide Gel Gene Therapy - methods Gene Transfer Techniques Genetic Vectors Green Fluorescent Proteins Hippocampus - pathology; virology Humans

Humans Immunohistochemistry Luminescent Proteins - metabolism Microscopy, Fluorescence Mutagenesis, Site-Directed Neurons - metabolism; virology Point Mutation Rats Semliki forest virus - genetics Temperature Time Factors Transgenes

Associated Chemicals: Luminescent Proteins (0) ; Green Fluorescent Proteins (147336-22-9)

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