Professor Smolke's research program focuses on developing modular genetic platforms for programming information processing and control functions in living systems, resulting in transformative technologies for engineering, manipulating, and probing biological systems. She has pioneered the design and application of a broad class of RNA molecules, called RNA devices, that process and transmit user-specified input signals to targeted protein outputs, thereby linking molecular computation to gene expression. This technology has been extended to efficiently construct multi-input devices exhibiting various higher-order information processing functions, demonstrating combinatorial assembly of many information processing, transduction, and control devices from a smaller number of components. Her laboratory is applying these technologies to addressing key challenges in cellular therapeutics, targeted molecular therapies, and green biosynthesis strategies.

Academic Appointments

Honors & Awards

  • World Technology Award in Biotechnology (Individual), World Technology Network (2009)
  • Alfred P. Sloan Foundation Fellow, Alfred P. Sloan Foundation (2008)
  • National Science Foundation CAREER Award, National Science Foundation (2006)
  • Beckman Young Investigator Award, Arnold and Mabel Beckman Foundation (2005)
  • TR100, Top 100 Young Innovators of the World, Technology Review (2004)

Professional Education

  • Postdoctorate, UC Berkeley, Cell Biology (2003)
  • Ph.D., UC Berkeley, Chemical Engineering (2001)
  • B.S., USC, Chemical Engineering (1997)


Journal Articles

  • Molecular tools for chemical biotechnology. Current opinion in biotechnology Galanie, S., Siddiqui, M. S., Smolke, C. D. 2013; 24 (6): 1000-1009


    Biotechnological production of high value chemical products increasingly involves engineering in vivo multi-enzyme pathways and host metabolism. Recent approaches to these engineering objectives have made use of molecular tools to advance de novo pathway identification, tunable enzyme expression, and rapid pathway construction. Molecular tools also enable optimization of single enzymes and entire genomes through diversity generation and screening, whole cell analytics, and synthetic metabolic control networks. In this review, we focus on advanced molecular tools and their applications to engineered pathways in host organisms, highlighting the degree to which each tool is generalizable.

    View details for DOI 10.1016/j.copbio.2013.03.001

    View details for PubMedID 23528237

  • A yeast-based rapid prototype platform for gene control elements in mammalian cells BIOTECHNOLOGY AND BIOENGINEERING Wei, K. Y., Chen, Y. Y., Smolke, C. D. 2013; 110 (4): 1201-1210


    Programming genetic circuits in mammalian cells requires flexible, tunable, and user-tailored gene-control systems. However, most existing control systems are either mechanistically specific for microbial organisms or must be laboriously re-engineered to function in mammalian cells. Here, we demonstrate a ribozyme-based device platform that can be directly transported from yeast to mammalian cells in a "plug-and-play" manner. Ribozyme switches previously prototyped in yeast are shown to regulate gene expression in a predictable, ligand-responsive manner in human HEK 293, HeLa, and U2OS cell lines without any change to device sequence nor further optimization. The ribozyme-based devices, which exhibit activation ratios comparable to the best RNA-based regulatory devices demonstrated in mammalian cells to-date, retain their prescribed functions (ON or OFF switch), tunability of regulatory stringency, and responsiveness to different small-molecule inputs in mammalian hosts. Furthermore, we observe strong correlations of device performance between yeast and all mammalian cell lines tested (R(2) ?= 0.63-0.97). Our unique device architecture can therefore act as a rapid prototyping platform (RPP) based on a yeast chassis, providing a well-developed and genetically tractable system that supports rapid and high-throughput screens for generating gene-controllers with a broad range of functions in mammalian cells. This platform will accelerate development of mammalian gene-controllers for diverse applications, including cell-based therapeutics and cell-fate reprogramming.

    View details for DOI 10.1002/bit.24792

    View details for Web of Science ID 000315360100020

    View details for PubMedID 23184812

  • A versatile cis-blocking and trans-activation strategy for ribozyme characterization NUCLEIC ACIDS RESEARCH Kennedy, A. B., Liang, J. C., Smolke, C. D. 2013; 41 (2)


    Synthetic RNA control devices that use ribozymes as gene-regulatory components have been applied to controlling cellular behaviors in response to environmental signals. Quantitative measurement of the in vitro cleavage rate constants associated with ribozyme-based devices is essential for advancing the molecular design and optimization of this class of gene-regulatory devices. One of the key challenges encountered in ribozyme characterization is the efficient generation of full-length RNA from in vitro transcription reactions, where conditions generally lead to significant ribozyme cleavage. Current methods for generating full-length ribozyme-encoding RNA rely on a trans-blocking strategy, which requires a laborious gel separation and extraction step. Here, we develop a simple two-step gel-free process including cis-blocking and trans-activation steps to support scalable generation of functional full-length ribozyme-encoding RNA. We demonstrate our strategy on various types of natural ribozymes and synthetic ribozyme devices, and the cleavage rate constants obtained for the RNA generated from our strategy are comparable with those generated through traditional methods. We further develop a rapid, label-free ribozyme cleavage assay based on surface plasmon resonance, which allows continuous, real-time monitoring of ribozyme cleavage. The surface plasmon resonance-based characterization assay will complement the versatile cis-blocking and trans-activation strategy to broadly advance our ability to characterize and engineer ribozyme-based devices.

    View details for DOI 10.1093/nar/gks1036

    View details for Web of Science ID 000314121100008

    View details for PubMedID 23155065

  • Synthetic Biology: Advancing the Design of Diverse Genetic Systems ANNUAL REVIEW OF CHEMICAL AND BIOMOLECULAR ENGINEERING, VOL 4 Wang, Y., Wei, K. Y., Smolke, C. D. 2013; 4: 69-102


    A major objective of synthetic biology is to make the process of designing genetically encoded biological systems more systematic, predictable, robust, scalable, and efficient. Examples of genetic systems in the field vary widely in terms of operating hosts, compositional approaches, and network complexity, ranging from simple genetic switches to search-and-destroy systems. While significant advances in DNA synthesis capabilities support the construction of pathway- and genome-scale programs, several design challenges currently restrict the scale of systems that can be reasonably designed and implemented. Thus, while synthetic biology offers much promise in developing systems to address challenges faced in the fields of manufacturing, environment and sustainability, and health and medicine, the realization of this potential is currently limited by the diversity of available parts and effective design frameworks. As researchers make progress in bridging this design gap, advances in the field hint at ever more diverse applications for biological systems. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering Volume 4 is June 07, 2013. Please see for revised estimates.

    View details for DOI 10.1146/annurev-chembioeng-061312-103351

    View details for Web of Science ID 000321740100005

    View details for PubMedID 23413816

  • Identification and treatment of heme depletion attributed to overexpression of a lineage of evolved P450 monooxygenases PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Michener, J. K., Nielsen, J., Smolke, C. D. 2012; 109 (47): 19504-19509


    Recent advances in metabolic engineering have demonstrated that microbial biosynthesis can provide a viable alternative to chemical synthesis for the production of bulk and fine chemicals. Introduction of a new biosynthetic pathway typically requires the expression of multiple heterologous enzymes in the production host, which can impose stress on the host cell and, thereby, limit performance of the pathway. Unfortunately, analysis and treatment of the host stress response can be difficult, because there are many sources of stress that may interact in complex ways. We use a systems biological approach to analyze the stress imposed by expressing different enzyme variants from a lineage of soluble P450 monooxygenases, previously evolved for heterologous activity in Saccharomyces cerevisiae. Our analysis identifies patterns of stress imposed on the host by heterologous enzyme overexpression that are consistent across the evolutionary lineage, ultimately implicating heme depletion as the major stress. We show that the monooxygenase evolution, starting from conditions of either high or low stress, caused the cellular stress to converge to a common level. Overexpression of rate-limiting enzymes in the endogenous heme biosynthetic pathway alleviates the stress imposed by expression of the P450 monooxygenases and increases the enzymatic activity of the final evolved P450 by an additional 2.3-fold. Heme overexpression also increases the total activity of an endogenous cytosolic heme-containing catalase but not a heterologous P450 that is membrane-associated. This work demonstrates the utility of combining systems and synthetic biology to analyze and optimize heterologous enzyme expression.

    View details for DOI 10.1073/pnas.1212287109

    View details for Web of Science ID 000311997200094

    View details for PubMedID 23129650

  • A high-throughput, quantitative cell-based screen for efficient tailoring of RNA device activity NUCLEIC ACIDS RESEARCH Liang, J. C., Chang, A. L., Kennedy, A. B., Smolke, C. D. 2012; 40 (20)


    Recent advances have demonstrated the use of RNA-based control devices to program sophisticated cellular functions; however, the efficiency with which these devices can be quantitatively tailored has limited their broader implementation in cellular networks. Here, we developed a high-efficiency, high-throughput and quantitative two-color fluorescence-activated cell sorting-based screening strategy to support the rapid generation of ribozyme-based control devices with user-specified regulatory activities. The high-efficiency of this screening strategy enabled the isolation of a single functional sequence from a library of over 10(6) variants within two sorting cycles. We demonstrated the versatility of our approach by screening large libraries generated from randomizing individual components within the ribozyme device platform to efficiently isolate new device sequences that exhibit increased in vitro cleavage rates up to 10.5-fold and increased in vivo activation ratios up to 2-fold. We also identified a titratable window within which in vitro cleavage rates and in vivo gene-regulatory activities are correlated, supporting the importance of optimizing RNA device activity directly in the cellular environment. Our two-color fluorescence-activated cell sorting-based screen provides a generalizable strategy for quantitatively tailoring genetic control elements for broader integration within biological networks.

    View details for DOI 10.1093/nar/gks636

    View details for Web of Science ID 000310970700002

    View details for PubMedID 22810204

  • Synthetic RNA switches as a tool for temporal and spatial control over gene expression CURRENT OPINION IN BIOTECHNOLOGY Chang, A. L., Wolf, J. J., Smolke, C. D. 2012; 23 (5): 679-688


    The engineering of biological systems offers significant promise for advances in areas including health and medicine, chemical synthesis, energy production, and environmental sustainability. Realizing this potential requires tools that enable design of sophisticated genetic systems. The functional diversity of RNA makes it an attractive and versatile substrate for programming sensing, information processing, computation, and control functions. Recent advances in the design of synthetic RNA switches capable of detecting and responding to molecular and environmental signals enable dynamic modulation of gene expression through diverse mechanisms, including transcription, splicing, stability, RNA interference, and translation. Furthermore, implementation of these switches in genetic circuits highlights the potential for building synthetic cell systems targeted to applications in environmental remediation and next-generation therapeutics and diagnostics.

    View details for DOI 10.1016/j.copbio.2012.01.005

    View details for Web of Science ID 000310406700007

    View details for PubMedID 22305712

  • High-throughput enzyme evolution in Saccharomyces cerevisiae using a synthetic RNA switch METABOLIC ENGINEERING Michener, J. K., Smolke, C. D. 2012; 14 (4): 306-316


    Metabolic engineering can produce a wide range of bulk and fine chemicals using renewable resources. These approaches frequently require high levels of activity from multiple heterologous enzymes. Directed evolution techniques have been used to improve the activity of a wide range of enzymes but can be difficult to apply when the enzyme is used in whole cells. To address this limitation, we developed generalizable in vivo biosensors using engineered RNA switches to link metabolite concentrations and GFP expression levels in living cells. Using such a sensor, we quantitatively screened large enzyme libraries in high throughput based on fluorescence, either in clonal cultures or in single cells by fluorescence activated cell sorting (FACS). By iteratively screening libraries of a caffeine demethylase, we identified beneficial mutations that ultimately increased the enzyme activity in vivo by 33 fold and the product selectivity by 22 fold. As aptamer selection strategies allow RNA switches to be readily adapted to recognize new small molecules, these RNA-based screening techniques are applicable to a broad range of enzymes and metabolic pathways.

    View details for DOI 10.1016/j.ymben.2012.04.004

    View details for Web of Science ID 000305275600003

    View details for PubMedID 22554528

  • Applications of genetically-encoded biosensors for the construction and control of biosynthetic pathways METABOLIC ENGINEERING Michener, J. K., Thodey, K., Liang, J. C., Smolke, C. D. 2012; 14 (3): 212-222


    Cells are filled with biosensors, molecular systems that measure the state of the cell and respond by regulating host processes. In much the same way that an engineer would monitor a chemical reactor, the cell uses these sensors to monitor changing intracellular environments and produce consistent behavior despite the variable environment. While natural systems derive a clear benefit from pathway regulation, past research efforts in engineering cellular metabolism have focused on introducing new pathways and removing existing pathway regulation. Synthetic biology is a rapidly growing field that focuses on the development of new tools that support the design, construction, and optimization of biological systems. Recent advances have been made in the design of genetically-encoded biosensors and the application of this class of molecular tools for optimizing and regulating heterologous pathways. Biosensors to cellular metabolites can be taken directly from natural systems, engineered from natural sensors, or constructed entirely in vitro. When linked to reporters, such as antibiotic resistance markers, these metabolite sensors can be used to report on pathway productivity, allowing high-throughput screening for pathway optimization. Future directions will focus on the application of biosensors to introduce feedback control into metabolic pathways, providing dynamic control strategies to increase the efficient use of cellular resources and pathway reliability.

    View details for DOI 10.1016/j.ymben.2011.09.004

    View details for Web of Science ID 000302876000005

    View details for PubMedID 21946159

  • Synthetic biology: Emerging methodologies to catalyze the metabolic engineering design cycle METABOLIC ENGINEERING Smolke, C. D., Tyo, K. E. 2012; 14 (3): 187-188

    View details for DOI 10.1016/j.ymben.2012.03.009

    View details for Web of Science ID 000302876000001

    View details for PubMedID 22465683

  • Advancing secondary metabolite biosynthesis in yeast with synthetic biology tools FEMS YEAST RESEARCH Siddiqui, M. S., Thodey, K., Trenchard, I., Smolke, C. D. 2012; 12 (2): 144-170


    Secondary metabolites are an important source of high-value chemicals, many of which exhibit important pharmacological properties. These valuable natural products are often difficult to synthesize chemically and are commonly isolated through inefficient extractions from natural biological sources. As such, they are increasingly targeted for production by biosynthesis from engineered microorganisms. The budding yeast species Saccharomyces cerevisiae has proven to be a powerful microorganism for heterologous expression of biosynthetic pathways. S. cerevisiae's usefulness as a host organism is owed in large part to the wealth of knowledge accumulated over more than a century of intense scientific study. Yet many challenges are currently faced in engineering yeast strains for the biosynthesis of complex secondary metabolite production. However, synthetic biology is advancing the development of new tools for constructing, controlling, and optimizing complex metabolic pathways in yeast. Here, we review how the coupling between yeast biology and synthetic biology is advancing the use of S. cerevisiae as a microbial host for the construction of secondary metabolic pathways.

    View details for DOI 10.1111/j.1567-1364.2011.00774.x

    View details for Web of Science ID 000300500100005

    View details for PubMedID 22136110

  • Synthetic biology: advancing biological frontiers by building synthetic systems GENOME BIOLOGY Chen, Y. Y., Galloway, K. E., Smolke, C. D. 2012; 13 (2)


    Advances in synthetic biology are contributing to diverse research areas, from basic biology to biomanufacturing and disease therapy. We discuss the theoretical foundation, applications, and potential of this emerging field.

    View details for DOI 10.1186/gb-2012-13-2-240

    View details for Web of Science ID 000305391700014

    View details for PubMedID 22348749

  • From DNA to Targeted Therapeutics: Bringing Synthetic Biology to the Clinic SCIENCE TRANSLATIONAL MEDICINE Chen, Y. Y., Smolke, C. D. 2011; 3 (106)


    Synthetic biology aims to make biological engineering more scalable and predictable, lowering the cost and facilitating the translation of synthetic biological systems to practical applications. Increasingly sophisticated, rationally designed synthetic systems that are capable of complex functions pave the way to translational applications, including disease diagnostics and targeted therapeutics. Here, we provide an overview of recent developments in synthetic biology in the context of translational research and discuss challenges at the interface between synthetic biology and clinical medicine.

    View details for DOI 10.1126/scitranslmed.3002944

    View details for Web of Science ID 000296586100002

    View details for PubMedID 22030748

  • Synthetic RNA modules for fine-tuning gene expression levels in yeast by modulating RNase III activity NUCLEIC ACIDS RESEARCH Babiskin, A. H., Smolke, C. D. 2011; 39 (19): 8651-8664


    The design of synthetic gene networks requires an extensive genetic toolbox to control the activities and levels of protein components to achieve desired cellular functions. Recently, a novel class of RNA-based control modules, which act through post-transcriptional processing of transcripts by directed RNase III (Rnt1p) cleavage, were shown to provide predictable control over gene expression and unique properties for manipulating biological networks. Here, we increase the regulatory range of the Rnt1p control elements, by modifying a critical region for enzyme binding to its hairpin substrates, the binding stability box (BSB). We used a high throughput, cell-based selection strategy to screen a BSB library for sequences that exhibit low fluorescence and thus high Rnt1p processing efficiencies. Sixteen unique BSBs were identified that cover a range of protein expression levels, due to the ability of the sequences to affect the hairpin cleavage rate and to form active cleavable complexes with Rnt1p. We further demonstrated that the activity of synthetic Rnt1p hairpins can be rationally programmed by combining the synthetic BSBs with a set of sequences located within a different region of the hairpin that directly modulate cleavage rates, providing a modular assembly strategy for this class of RNA-based control elements.

    View details for DOI 10.1093/nar/gkr445

    View details for Web of Science ID 000296341100036

    View details for PubMedID 21737428

  • Engineering Biological Systems with Synthetic RNA Molecules MOLECULAR CELL Liang, J. C., Bloom, R. J., Smolke, C. D. 2011; 43 (6): 915-926


    RNA molecules play diverse functional roles in natural biological systems. There has been growing interest in designing synthetic RNA counterparts for programming biological function. The design of synthetic RNA molecules that exhibit diverse activities, including sensing, regulatory, information processing, and scaffolding activities, has highlighted the advantages of RNA as a programmable design substrate. Recent advances in implementing these engineered RNA molecules as key control elements in synthetic genetic networks are highlighting the functional relevance of this class of synthetic elements in programming cellular behaviors.

    View details for DOI 10.1016/j.molcel.2011.08.023

    View details for Web of Science ID 000295309800007

    View details for PubMedID 21925380

  • Cell biology. Bringing it together with RNA. Science Thodey, K., Smolke, C. D. 2011; 333 (6041): 412-413

    View details for DOI 10.1126/science.1209685

    View details for Web of Science ID 000292959600031

    View details for PubMedID 21778388

  • Engineering ligand-responsive RNA controllers in yeast through the assembly of RNase III tuning modules NUCLEIC ACIDS RESEARCH Babiskin, A. H., Smolke, C. D. 2011; 39 (12): 5299-5311


    The programming of cellular networks to achieve new biological functions depends on the development of genetic tools that link the presence of a molecular signal to gene-regulatory activity. Recently, a set of engineered RNA controllers was described that enabled predictable tuning of gene expression in the yeast Saccharomyces cerevisiae through directed cleavage of transcripts by an RNase III enzyme, Rnt1p. Here, we describe a strategy for building a new class of RNA sensing-actuation devices based on direct integration of RNA aptamers into a region of the Rnt1p hairpin that modulates Rnt1p cleavage rates. We demonstrate that ligand binding to the integrated aptamer domain is associated with a structural change sufficient to inhibit Rnt1p processing. Three tuning strategies based on the incorporation of different functional modules into the Rnt1p switch platform were demonstrated to optimize switch dynamics and ligand responsiveness. We further demonstrated that these tuning modules can be implemented combinatorially in a predictable manner to further improve the regulatory response properties of the switch. The modularity and tunability of the Rnt1p switch platform will allow for rapid optimization and tailoring of this gene control device, thus providing a useful tool for the design of complex genetic networks in yeast.

    View details for DOI 10.1093/nar/gkr090

    View details for Web of Science ID 000292564900041

    View details for PubMedID 21355039

  • Design of small molecule-responsive microRNAs based on structural requirements for Drosha processing NUCLEIC ACIDS RESEARCH Beisel, C. L., Chen, Y. Y., Culler, S. J., Hoff, K. G., Smolke, C. D. 2011; 39 (7): 2981-2994


    MicroRNAs (miRNAs) are prevalent regulatory RNAs that mediate gene silencing and play key roles in diverse cellular processes. While synthetic RNA-based regulatory systems that integrate regulatory and sensing functions have been demonstrated, the lack of detail on miRNA structure-function relationships has limited the development of integrated control systems based on miRNA silencing. Using an elucidated relationship between Drosha processing and the single-stranded nature of the miRNA basal segments, we developed a strategy for designing ligand-responsive miRNAs. We demonstrate that ligand binding to an aptamer integrated into the miRNA basal segments inhibits Drosha processing, resulting in titratable control over gene silencing. The generality of this control strategy was shown for three aptamer-small molecule ligand pairs. The platform can be extended to the design of synthetic miRNAs clusters, cis-acting miRNAs and self-targeting miRNAs that act both in cis and trans, enabling fine-tuning of the regulatory strength and dynamics. The ability of our ligand-responsive miRNA platform to respond to user-defined inputs, undergo regulatory performance tuning and display scalable combinatorial control schemes will help advance applications in biological research and applied medicine.

    View details for DOI 10.1093/nar/gkq954

    View details for Web of Science ID 000289628400050

    View details for PubMedID 21149259

  • Informing Biological Design by Integration of Systems and Synthetic Biology CELL Smolke, C. D., Silver, P. A. 2011; 144 (6): 855-859


    Synthetic biology aims to make the engineering of biology faster and more predictable. In contrast, systems biology focuses on the interaction of myriad components and how these give rise to the dynamic and complex behavior of biological systems. Here, we examine the synergies between these two fields.

    View details for DOI 10.1016/j.cell.2011.02.020

    View details for Web of Science ID 000288543500004

    View details for PubMedID 21414477

  • A synthetic library of RNA control modules for predictable tuning of gene expression in yeast MOLECULAR SYSTEMS BIOLOGY Babiskin, A. H., Smolke, C. D. 2011; 7


    Advances in synthetic biology have resulted in the development of genetic tools that support the design of complex biological systems encoding desired functions. The majority of efforts have focused on the development of regulatory tools in bacteria, whereas fewer tools exist for the tuning of expression levels in eukaryotic organisms. Here, we describe a novel class of RNA-based control modules that provide predictable tuning of expression levels in the yeast Saccharomyces cerevisiae. A library of synthetic control modules that act through posttranscriptional RNase cleavage mechanisms was generated through an in vivo screen, in which structural engineering methods were applied to enhance the insulation and modularity of the resulting components. This new class of control elements can be combined with any promoter to support titration of regulatory strategies encoded in transcriptional regulators and thus more sophisticated control schemes. We applied these synthetic controllers to the systematic titration of flux through the ergosterol biosynthesis pathway, providing insight into endogenous control strategies and highlighting the utility of this control module library for manipulating and probing biological systems.

    View details for DOI 10.1038/msb.2011.4

    View details for Web of Science ID 000289205600006

    View details for PubMedID 21364573

  • Reprogramming Cellular Behavior with RNA Controllers Responsive to Endogenous Proteins SCIENCE Culler, S. J., Hoff, K. G., Smolke, C. D. 2010; 330 (6008): 1251-1255


    Synthetic genetic devices that interface with native cellular pathways can be used to change natural networks to implement new forms of control and behavior. The engineering of gene networks has been limited by an inability to interface with native components. We describe a class of RNA control devices that overcome these limitations by coupling increased abundance of particular proteins to targeted gene expression events through the regulation of alternative RNA splicing. We engineered RNA devices that detect signaling through the nuclear factor ?B and Wnt signaling pathways in human cells and rewire these pathways to produce new behaviors, thereby linking disease markers to noninvasive sensing and reprogrammed cellular fates. Our work provides a genetic platform that can build programmable sensing-actuation devices enabling autonomous control over cellular behavior.

    View details for DOI 10.1126/science.1192128

    View details for Web of Science ID 000284613700044

    View details for PubMedID 21109673

  • Genetic control of mammalian T-cell proliferation with synthetic RNA regulatory systems PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Chen, Y. Y., Jensen, M. C., Smolke, C. D. 2010; 107 (19): 8531-8536


    RNA molecules perform diverse regulatory functions in natural biological systems, and numerous synthetic RNA-based control devices that integrate sensing and gene-regulatory functions have been demonstrated, predominantly in bacteria and yeast. Despite potential advantages of RNA-based genetic control strategies in clinical applications, there has been limited success in extending engineered RNA devices to mammalian gene-expression control and no example of their application to functional response regulation in mammalian systems. Here we describe a synthetic RNA-based regulatory system and its application in advancing cellular therapies by linking rationally designed, drug-responsive, ribozyme-based regulatory devices to growth cytokine targets to control mouse and primary human T-cell proliferation. We further demonstrate the ability of our synthetic controllers to effectively modulate T-cell growth rate in response to drug input in vivo. Our RNA-based regulatory system exhibits unique properties critical for translation to therapeutic applications, including adaptability to diverse ligand inputs and regulatory targets, tunable regulatory stringency, and rapid response to input availability. By providing tight gene-expression control with customizable ligand inputs, RNA-based regulatory systems can greatly improve cellular therapies and advance broad applications in health and medicine.

    View details for DOI 10.1073/pnas.1001721107

    View details for Web of Science ID 000277591200010

    View details for PubMedID 20421500

  • Building outside of the box: iGEM and the BioBricks Foundation NATURE BIOTECHNOLOGY Smolke, C. D. 2009; 27 (12): 1099-1102

    View details for DOI 10.1038/nbt1209-1099

    View details for Web of Science ID 000272708300020

    View details for PubMedID 20010584

  • Cell biology. It's the DNA that counts. Science Smolke, C. D. 2009; 324 (5931): 1156-1157

    View details for DOI 10.1126/science.1174843

    View details for PubMedID 19478174

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