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The Impact of Mammalian Gene Regulation Concepts on Functional Genomic Research, Metabolic Engineering, and Advanced Gene Therapies
Author(s) -
Fussenegger Martin
Publication year - 2001
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1021/bp000129c
Subject(s) - transactivation , biology , functional genomics , computational biology , gene , regulation of gene expression , transgene , gene expression , promoter , heterologous expression , gene regulatory network , transcriptional regulation , genomics , genetics , genome , recombinant dna
Regulation of heterologous gene expression is of prime importance for a wide variety of basic and applied biological research areas including functional genomics, tissue engineering, gene therapy, and biopharmaceutical manufacturing. Initial gene regulation strategies employed endogenous responsive elements, which resulted in pleiotropic interference of transgene expression with host regulatory networks. Current regulation systems are binary and consist of chimeric transactivators and responsive target promoters of heterologous bacterial or insect origin, or they contain artificially designed components. Regulation of generic systems is based on binding of a transactivator to its cognate promoter, which is modulated by specific molecules such as antibiotics or hormones and brings the transactivation domain into contact with a minimal promoter, thereby inducing target gene expression. Binary gene regulation concepts have been significantly refined in recent years with a focus to improve their regulation performance and their compatibility with human‐therapeutic use. In this review we present a detailed analysis of currently available mammalian gene regulation systems and document progress that has pioneered the use of such systems in various aspects of human therapy.