A Cascade of Synthetic Logic Gates for Differentiated Anti-mitotic Cancer Therapy
Date Issued
2016
Date
2016
Author(s)
Lian, Bo-Han
Abstract
Chemotherapy is a conventional treatment for cancer. Traditional chemotherapeutic agents are cytotoxic to dividing cells by means of interfering with mitosis but without specific targeting and often cause side effects and frequent failures. Myelosuppression due to destruction of dividing hematopoietic stem cells (HSCs) in bone marrow is one of the side effects for anti-mitotic chemotherapy. When myelosuppression is severe, it may lead to neutropenia and often company with infections that will threaten patient’s life. An alternative way to overcome this side effect is using gene therapy. With a “synthetic biology” approach, we construct a synthetic genetic circuit that cytotoxic to proliferating tumor cells and spare hematopoietic stem cells. The circuit based on RNA interference (RNAi) and tetracycline-controllable expression system is able to detect and respond to cellular information from cyclin B1 promoter and miR-142 microRNA binding site (MBS) in individual cells. All units of circuit were validated its performance by using fluorescence protein as reporter and then cascaded into layers of logic gates with optimizing feedback/feed-forward loops. Here we present a synthetic logic genetic circuit targeting and killing proliferating tumor cells in vitro. This study provides a potential strategy for cancer gene therapy.
Subjects
cancer
anti-mitotic
gene therapy
synthetic biology
RNA interference
SDGs
Type
thesis