Gene transfer: the challenge of regulated gene expression.
Gene therapy is expected to have a major impact on human healthcare in the future. However, precise regulation of therapeutic gene expression in vivo is still a challenge. Natural and synthetic enhancer-promoters (EPs) can be utilized to drive gene transcription in a temporal, spatial or environmental signal-inducible manner in response to heat shock, hypoxia, radiation, chemotherapy, epigenetic agents or viral infection. To allow tightly regulated expression, a regulatable gene-expression system can also be implemented. Most of these systems are based on small molecule (drug)-responsive artificial transactivators. In this review, we aim to provide a brief overview of the classes of EPs and regulatable systems, along with lessons learned from these studies. We highlight the potential applications in gene transfer, gene therapy for cancer and genetic disease and the future challenges for clinical applications.
Guo
Z Sheng
ZS
Division of Surgical Oncology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. guozs@upmc.edu
Li
Qiang
Q
Bartlett
David L
DL
Yang
James Y
JY
Fang
Bingliang
B
D000818:Animals; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism; D014158:Transcription, Genetic