Inducible Vector Systems Design for Lentiviral Vector
Lentiviral vectors have emerged as safe and effective delivery vehicles for clinical gene therapy, particularly for monogenic recessive disorders. As a world-class biotechnology company, Creative Biolabs provides omnidirectional technologies to meet the diverse needs of our clients. With our professional experience and advanced lentiviral vector design platform, we are therefore confident in offering the best service for the treatment of a range of diseases.
Introduction of Inducible Lentiviral Vector Systems
Lentiviral vectors can be used for externally controllable transgene expression. Among several inducible systems, the rtTA (reverse tetracycline-controlled transactivator)-regulated system has been widely used for inducible gene expression. This system uses a chimaeric transcription factor tTA transactivator, a fusion protein between the bacterial TetR with the activating domain of herpes simplex virus VP16, or its derivative rtTA protein, along with a TetO-binding-sites-containing promoter for tetracycline-induced gene silencing (Tet-Off) or activation (Tet-On) respectively. The Tet-On/Tet-Off systems have been studied extensively in the context of lentiviral vectors, in which the Tet-regulated system is incorporated into a single lentiviral vector. Recent developments in the Tet-On/Tet-Off systems allow selective induction and repression of different transgenes from a single inducible cassette, which reduces the leakiness of the system and improves the ability to control transgene expression. Based on the advantages of this system, we choose to incorporate it into the lentiviral vector system and investigate its ability to deliver and regulate transgene expression in vitro and in vivo.
Figure 1. Tetracycline activator system (rtTA; "Tet-on").
Another common inducible vector system is to regulate expression by using a vector that is activated by endogenous, pathophysiological stimulus, such as hypoxia or oxidative stress. Hypoxia-regulated gene therapy vectors using tandem repeats of hypoxia response elements (HREs), enhancer regions in the promoters of genes activated during hypoxia, have been developed and used to regulate expression of the HO-1 transgene in vectors used for cardioprotection against I/R injury. Studies have shown that ARE sequences can be exploited for the development of oxidative stress-inducible gene therapy vectors. In human endothelial cells, ARE driven HO-1 overexpression inhibited nuclear factor-κB activation and subsequent vascular cell adhesion molecule-1 expression induced by tumor necrosis factor-α.
The Service of Inducible Lentiviral Vector Construction
Progress in gene therapy has allowed the development of several strategies against human diseases. Inducible lentiviral vectors are excellent tools to transfer genes into cells. To date, we have successfully developed a variety of inducible lentiviral vector systems, including tetracycline-inducible system, doxycycline-inducible system, and oxidative stress-inducible system.
Creative Biolabs has long-term devoted to the design methods of lentiviral vector. With years of experience, our scientists have developed several lentiviral vector design platforms to boost our global customers' research and project goals. We are pleased to use our extensive experience and advanced platform to offer the best service and the most qualified products to satisfy the diverse needs from our customers. If you are interested in our services, please contact us or send us an inquiry.
