An Autogenously Regulated Expression System for Gene Therapeutic Ocular Applications

作者：Sochor Matthew A; Vasireddy Vidyullatha; Drivas Theodore G; Wojno Adam; Doung Thu; Shpylchak Ivan; Bennicelli Jeannette; Chung Daniel; Bennett Jean^*; Lewis Mitchell

来源：Scientific Reports, 2015, 5(1): 17105.

DOI：10.1038/srep17105

The future of treating inherited and acquired genetic diseases will be defined by our ability to introduce transgenes into cells and restore normal physiology. Here we describe an autogenous transgene regulatory system (ARES), based on the bacterial lac repressor, and demonstrate its utility for controlling the expression of a transgene in bacteria, eukaryotic cells, and in the retina of mice. This ARES system is inducible by the small non-pharmacologic molecule, Isopropyl beta-D-1-thiogalactopyranoside (IPTG) that has no off-target effects in mammals. Following subretinal injection of an adeno-associated virus (AAV) vector encoding ARES, luciferase expression can be reversibly controlled in the murine retina by oral delivery of IPTG over three induction-repression cycles. The ability to induce transgene expression repeatedly via administration of an oral inducer in vivo, suggests that this type of regulatory system holds great promise for applications in human gene therapy.

• 出版日期2015-11-24