FAST-STEM: Synthetic Biology Toolkit for Next Generation Regenerative Medicine

Aaron H. Rosenstein, Andrew Chai, Nitya Gulati, Ting Yin, Maria Nguyen, Danielle Serra, Tania Devina, Aanshi Gandhi, Mohammad Saleh, Penney Gilbert, Michael A. Laflamme, Shinichiro Ogawa, Julien Muffat, Yun Li, Stephanie Protze, Tilo Kunath, Sneak Peek Administrator, Michael Garton, Rangarajan Sambathkumar, Brandon M. MurareanuNavroop K. Dhaliwal, Fumao Sun, Xinyaun Zhao, Abolfazl Dadvar, Rasha Al-attar

Research output: Working paperPreprint

Abstract

Very recent clinical advancements in human stem cell (hPSC) based tissue replacement have opened a new frontier of possibility: therapeutically augmented human cell engraftment. Therapeutic augmentation requires the design of synthetic gene circuits that are compatible with hPSCs. Such design is highly challenging due to: (a) poor translation of circuits developed in immortalized cell lines; (b) absence of effective tools for synthetic human stem cell development. To address this, we developed FAST-STEM (Facile Accelerated Stem-cell Transgene integration with SynBio Tunable Engineering Modes), a platform that enables design–build–test–learn style hPSC engineering. FAST-STEM facilitates fast iterative synthetic cell evolution, zygosity manipulation, and highly controlled library screening. Differentiation ready synthetic stem cells can be generated an-order-of-magnitude faster by FAST-STEM than by current site-specific methods. We demonstrate FAST-STEM potential to revolutionize human synthetic biology, by creation of synthetic human liver, glial-cells, muscle, cardiomyocytes, pancreatic beta-cells, cortical neurons, and dopaminergic neurons. 

Original languageEnglish
Place of Publicationhttps://papers.ssrn.com/
PublisherElsevier
DOIs
Publication statusUnpublished - 24 Jul 2024

Publication series

NameCELL-D-24-02515

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