Synthetic Gene Expression Circuits for Designing Precision Tools in Oncology

Abstract

Precision medicine in oncology needs to enhance its capabilities to match diagnostic and therapeutic technologies to individual patients. Synthetic biology streamlines the design and construction of functionalized devices through standardization and rational engineering of basic biological elements decoupled from their natural context. Remarkable improvements have opened the prospects for the availability of synthetic devices of enhanced mechanism clarity, robustness, sensitivity, as well as scalability and portability, which might bring new capabilities in precision cancer medicine implementations. In this review, we begin by presenting a brief overview of some of the major advances in the engineering of synthetic genetic circuits aimed to the control of gene expression and operating at the transcriptional, post-transcriptional/translational, and post-translational levels. We then focus on engineering synthetic circuits as an enabling methodology for the successful establishment of precision technologies in oncology. We describe significant advancements in our capabilities to tailor synthetic genetic circuits to specific applications in tumor diagnosis, tumor cell- and gene-based therapy, and drug delivery.

Keywords: biological engineering; drug delivery; drug discovery; precision medicine; synthetic biology; synthetic circuit; tumor diagnosis; tumor therapy.

Figure 1

Biological engineering enacts precision tools in oncology. (A) The synthetic biology toolbox contains a variety of regulatory switches which allow gene expression control at transcriptional, post-transcriptional, translational, and post-translational levels. (B) Abstraction hierarchy used for synthetic circuit design and construction. The hierarchy includes: parts, which are endowed with basic biological functions, devices, which are any combination of parts that perform a human-defined function, and systems, which are any combination of devices. (C) Overview of synthetic circuits' applications ranging from drug discovery to tumor diagnosis and to tumor therapy relevant to precision oncology interventions.