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Zilberzwige-Tal, S.

Publications and source records attributed to Zilberzwige-Tal, S..

2 recordsLinked to original sources

Investigating And Modeling the Factors that Effects the Performance of Genetic Circuits

Over the past two decades, synthetic biology has yielded ever more complex genetic circuits able to perform sophisticated functions in response to specific signals. Yet, genetic circuits are not immediately transferable to an outside-the-lab setting where their performance is highly compromised. We propose introducing a scale step to the design-build-test workflow to include factors that might contribute to unexpected genetic circuit performance. As a proof-of-concept, we designed and tested a genetic circuit under different temperatures, mediums, inducer concentrations, and bacterial growth phases. We determined that the circuits performance is dramatically altered when these factors differ from the optimal lab conditions. Based on these results, a scaling effort, coupled with a learning process, proceeded to generate model predictions for the genetic circuits performance under untested conditions, which is currently lacking in synthetic biology application design. As the synthetic biology discipline transitions from proof-of-concept genetic programs to appropriate and safe application implementations, more emphasis on a scale step is needed to ensure correct and robust performances.

synthetic biology↗

Engineered Riboswitch Nano-carriers as a Possible Disease-Modifying Treatment for Metabolic Disorders

Both DNA- and RNA-based nanotechnologies are remarkably useful for in vitro molecular-scale device engineering and are applied in a vast array of applications. However, while the function of nucleic acid nanostructures is robust under in vitro settings, their implementation in real-world conditions requires overcoming their inherent degradation sensitivity and subsequent loss of function. Viruses are minimalistic yet sophisticated supramolecular assemblies, able to protect their nucleic acid content in inhospitable biological environments. Inspired by this natural ability, we engineered RNA-virus-like particles (VLPs) nanocarriers (NCs). We showed that the VLPs can serve as an excellent protective shell against nuclease-mediated degradation. We then harnessed biological recognition elements and demonstrated how engineered riboswitch NCs can act as a possible disease-modifying treatment for genetic metabolic disorders. The functional riboswitch is capable of selectively and specifically binding metabolites and preventing their self-assembly process and its downstream effects. When applying the riboswitch nano-carriers to an in vivo yeast model of adenine accumulation and self-assembly, significant inhibition of the sensitivity to adenine feeding was observed. In addition, using an amyloid-specific dye, we proved the riboswitch nano-carriers ability to reduce the level of intracellular amyloid-like cytotoxic structures. The potential of this RNA therapeutic technology does not stop at metabolic disorders, as it can be easily fine-tuned to be applied to other conditions and diseases.

bioengineering↗