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Conditional gene vectors regulated in cis.
Nucleic Acids Res. 36:e83 (2008)
Non-integrating gene vectors, which are stably and extrachromosomally maintained in transduced cells would be perfect tools to support long-term expression of therapeutic genes but preserve the genomic integrity of the cellular host. Small extrachromosomal plasmids share some of these ideal characteristics but are primarily based on virus blueprints. These plasmids are dependent on viral trans-acting factors but they can replicate their DNA molecules in synchrony with the chromosome of the cellular host and segregate to daughter cells in an autonomous fashion. On the basis of the concept of the latent origin of DNA replication of Epstein-Barr virus, oriP, we devised novel derivatives, which exclusively rely on an artificial replication factor for both nuclear retention and replication of plasmid DNA. In addition, an allosteric switch regulates the fate of the plasmid molecules, which are rapidly lost upon addition of doxycycline. Conditional maintenance of these novel plasmid vectors allows the reversible transfer of genetic information into target cells for the first time.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
EPSTEIN-BARR-VIRUS; ORIGIN RECOGNITION COMPLEX; ZINC-FINGER NUCLEASES; PACKAGING CELL-LINE; DNA-REPLICATION; MAMMALIAN-CELLS; INFECTIOUS DELIVERY; FLUORESCENT PROTEIN; PLASMID REPLICON; EPISOMAL VECTOR
ISSN (print) / ISBN
0305-1048
e-ISSN
1362-4962
Journal
Nucleic Acids Research
Quellenangaben
Volume: 36,
Issue: 13,
Article Number: e83
Publisher
Oxford University Press
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Research Unit Gene Vector (AGV)