Enhanced Vector Design for Cancer Gene Therapy with Hierarchical Enhancement of Therapeutic Transgene Expression

A set of vectors for Cre recombinase-dependent expression of the hybrid suicidal FCU1 transgene was constructed, including a two-plasmid system wherein the FCU1 and Cre transgenes reside in separate vectors, and single-plasmid variants in which a single plasmid bears both transgenes. To improve the...

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Veröffentlicht in:Human gene therapy. Part B. Methods 2017-10, Vol.28 (5), p.247-254
Hauptverfasser: Kostina, M B, Sass, A V, Stukacheva, E A, Korobko, I V, Sverdlov, E D
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container_end_page 254
container_issue 5
container_start_page 247
container_title Human gene therapy. Part B. Methods
container_volume 28
creator Kostina, M B
Sass, A V
Stukacheva, E A
Korobko, I V
Sverdlov, E D
description A set of vectors for Cre recombinase-dependent expression of the hybrid suicidal FCU1 transgene was constructed, including a two-plasmid system wherein the FCU1 and Cre transgenes reside in separate vectors, and single-plasmid variants in which a single plasmid bears both transgenes. To improve the safety profile and specificity in cancer gene therapy applications, as well as to ensure stable propagation of plasmids in bacterial cells, the Cre/LoxP system components were optimized. A bicistronic vector with the Cre expression cassette placed between the LoxP sites unidirectionally with FCU1 cDNA resulted in higher therapeutic efficiency compared with the double-plasmid system in an enzyme-prodrug suicide cancer gene therapy scheme. Therefore, the feasibility of a single-plasmid approach in the development of cancer gene therapy with hierarchical enhancement of therapeutic transgene expression has been demonstrated.
doi_str_mv 10.1089/hgtb.2016.170
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subjects Cell Line, Tumor
Genetic Therapy - methods
Genetic Vectors - genetics
Genetic Vectors - metabolism
Genetic Vectors - therapeutic use
Humans
Integrases - genetics
Neoplasms - therapy
Pentosyltransferases - genetics
Pentosyltransferases - metabolism
Transgenes - genetics
title Enhanced Vector Design for Cancer Gene Therapy with Hierarchical Enhancement of Therapeutic Transgene Expression
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