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.

Quantifying the distribution of protein oligomerization degree reflects cellular information capacity

“…The common rules underlying protein oligomerization distribution can help better understand biological processes in nature and reveal new design principles of cellular architecture. The challenging tasks of synthetic biology include scale-up protein network generation and robust computation performance for living cells for use in diagnostic, therapeutic and biotechnological applications 58 – 60 . Expanding our knowledge of protein oligomerization in the context of single molecules, multimolecular networks and whole cells will contribute to new levels of understanding of the critical roles that cooperativity play in the function of complex biological systems.…”

Engineering Molecular Machines for the Control of Cellular Functions for Diagnostics and Therapeutics

“…Furthermore, the incorporation of engineered bacteria into the gut microbiome as a therapeutic approach has been utilized for various applications such as aide in the digestion of phenylalanine and mitigate related diseases . These biological systems are engineered to be analogous to electrical circuits such that natural mechanisms of cellular function are harnessed to generate material capable of sensing and responding to intracellular and extracellular stimuli . In these cases, safety controls are incorporated into material design to ensure material stability.…”

“…Indeed, the manipulation of live cell genetics is evidenced by the generate material capable of sensing and responding to intracellular and extracellular stimuli. [13] In these cases, safety controls are incorporated into material design to ensure material stability. By incorporating multiple copies of engineered genes and integrating essential genes into introduced sequences, the circuits can be designed in a way such that genetic deletions or mutations would not compromise engineered function while insertions would result in a cell death.…”

Pulsed Electric Fields Alter Expression of NF-κB Promoter-Controlled Gene

“…The possibility to artificially adjust and fine-tune gene expression is one of the key milestones in contemporary bioengineering and synthetic biology [ 1 , 2 ]. In addition, gene expression control has become highly relevant for clinical applications with the rise of advanced targeted medicines such as cell-based therapies, protein drugs, or gene therapies [ 3 , 4 , 5 ]. Techniques of targeted therapeutics may provide treatment options that are beyond the reach of conventional small-molecule medicines [ 6 , 7 , 8 ].…”