Advances in genetic circuit design: novel biochemistries, deep part mining, and precision gene expression

A renaissance in RNA synthetic biology: new mechanisms, applications and tools for the future

“…RNA regulatory switches that respond to a range of small molecules, RNAs, and proteins have also been engineered [9][10][11]. While these examples highlight the versatility and designability of RNAs, RNA regulators have typically lagged behind protein regulators in terms of dynamic range and the number of independently acting, or orthogonal, regulators available for genetic circuit construction [1]. Recently, exciting new RNA-based regulatory mechanisms have been engineered that overcome these limitations.…”

“…Although synthetic RNA regulators were one of the early successes in this endeavor [2], historically there has been a greater emphasis placed on engineering protein regulators [3]. This is in part due to the large dynamic ranges of protein repressors and transcription factors, and the large repertoire of natural regulators to draw from [1]. Recently however, there has been a resurgence of interest in engineering and applying synthetic RNA regulators to control gene expression [4,5].…”

“…Remarkable progress has been made in creating libraries of genetic regulators that can be configured to control the expression of individual genes, or to implement advanced programs via genetic circuits [1]. Although synthetic RNA regulators were one of the early successes in this endeavor [2], historically there has been a greater emphasis placed on engineering protein regulators [3].…”

“…Therefore, our ability to engineer biological systems is directly related to our ability to control gene expression. Consequently, there has been a great deal of work within synthetic biology to develop versatile and programmable genetic regulators that enable the precise control of gene expression [1].…”

Synthetic protein switches: design principles and applications

“…This encompasses all levels of complexity, ranging from proteins to pathways, networks, and, ultimately, organisms, and has application for molecular diagnostics, cell-based biosensors, therapeutics, and industrial biotechnology [1,2]. In addition, a capacity to engineer biological signaling systems with predictable behavior provides ultimate proof to scientific models describing biological processes [1].Constructing artificial signaling systems has been realized predominantly with synthetic gene circuits, in which rational engineering strategies are supported by the modular organization and function of transcription factors and their DNA response elements [3,4]. Similarly, aptamers and ribozymes have been recombined to create functional nucleic acids that can sense and amplify distinct molecular cues [5] or exert post-transcriptional control on gene expression [6].…”