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Lentiviral vector system for coordinated constitutive and drug controlled tetracycline-regulated gene co-expression

Paper ID Volume ID Publish Year Pages File Format Full-Text
5621 406 2015 13 PDF Available
Title
Lentiviral vector system for coordinated constitutive and drug controlled tetracycline-regulated gene co-expression
Abstract

Constitutive co-expression of cooperating transgenes using retroviral integrating vectors is frequently used for genetic modification of different cell types to establish therapeutic or cancer models. However, such approaches are unable to dissect the influence of dose, order and reversibility of transgene expression on the fate of newly developed therapeutic/malignant phenotypes. We present a modular lentiviral vector system, which provides expression of constitutive and inducible components. To demonstrate its functionality, we constitutively expressed the well-described transcription factor Meis1 followed by inducible co-expression of collaborating partner Hoxa9 under the control of tetracycline responsive promoters in murine fibroblasts and primary hematopoietic progenitor cells (HPCs). Fluorescent markers to track transgene co-expression revealed tightly controlled, efficiently inducible and reversible but cell type dependent gene transfer over time. We demonstrated dose-dependent blockade of myeloid differentiation when both Meis1/Hoxa9 were concomitantly overexpressed in primary HPCs in vitro, but the absence of the transformed phenotype in non-induced samples or when Hoxa9 expression was down-regulated. This system combines the advantages of lentiviral gene transfer and the opportunity for drug-controlled co-expression of multiple transgenes to dissect, among others, gene networks governing complex cell behavior, such as proto-oncogene dose-dependent leukemogenic pathways or collaborating mechanisms of genes enhancing competitive fitness of hematopoietic cells.

Keywords
Lentiviral; Constitutive; Tetracycline-regulated; Multiple transgenes; Dose-dependent; Genetic modification of HSCs; Fate decision
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Lentiviral vector system for coordinated constitutive and drug controlled tetracycline-regulated gene co-expression
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 63, September 2015, Pages 189–201
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us