Sam Schaffter has been a chemical engineer at the National Institute of Standards and Technology (NIST) since 2020. His research focuses on developing an RNA-based computer for programming cellular behavior, with applications spanning biomanufacturing to precision medicine. Prior to joining NIST, Sam received his Ph.D. in chemical and biomolecular engineering from Johns Hopkins, exploring how to program nucleic acid-based nanomaterials. For his graduate work, he was awarded the 2021 Robert Dirks Molecular Programming Prize. Originally from Indiana, Sam obtained B.S. degrees in biological engineering and biochemistry from Purdue University.

Keynote Abstract

RNA strand exchange circuits as a general-purpose molecular programming language for synthetic biology

A major goal of synthetic biology is to program biological systems with the same precision with which we program electronic devices, ultimately enabling the next generation of diagnostics, therapeutics, and biotechnologies. Great strides have been made, but a general challenge is most molecular programming paradigms are developed to operate in a narrow set of environments or applications. Further, sensing, information processing, and signal transduction are often coupled within a single device or design, making interoperability difficult. In contrast, in electronic computing inputs are converted into a universal machine language for information processing, and outputs of the machine instructions are mapped back to an application specific response. This enables seamless communication and integration across devices and applications. To enable similarly broad programmability of biological systems, we are developing a molecular equivalent of these machine instructions based on genetically encoded RNA strand exchange circuits called ctRSD circuits. RNA strand exchange reactions are easily programmed via predictable base pairing interactions universal across cell types, enabling wide operability. Further, in vitro nucleic acid strand exchange reactions are one of the most scalable and programmable biomolecular systems to date, demonstrating, for example, neural network-based classification of hundreds of inputs. Towards the goal of a general-purpose molecular programming language, we have demonstrated ctRSD circuits operate predictably in in vitro transcription reactions, cell-free transcription and translation systems, and bacterial cells. To seamlessly convert from different chemical spaces into RNA strand exchange space for information processing, we are developing biosensors that transduce nucleic acid, metabolite, ion, and protein binding into RNA expression. Lastly, we are developing mechanisms to map out of RNA space to target different applications, so far demonstrating RNA strand exchange to precisely control protein expression. These results begin to demonstrate how general-purpose RNA strand exchange circuits can be used as a CPU for synthetic biology.