Abstract
Genetically engineering cells to perform customizable functions is an emerging frontier with numerous technological and translational applications. However, it remains challenging to systematically engineer mammalian cells to execute complex functions. To address this need, we developed a method enabling accurate genetic program design using high-performing genetic parts and predictive computational models. We built multifunctional proteins integrating both transcriptional and posttranslational control, validated models for describing these mechanisms, implemented digital and analog processing, and effectively linked genetic circuits with sensors for multi-input evaluations. The functional modularity and compositional versatility of these parts enable one to satisfy a given design objective via multiple synonymous programs. Our approach empowers bioengineers to predictively design mammalian cellular functions that perform as expected even at high levels of biological complexity.
| Original language | English (US) |
|---|---|
| Article number | eabe9375 |
| Journal | Science Advances |
| Volume | 7 |
| Issue number | 8 |
| DOIs | |
| State | Published - Feb 19 2021 |
Funding
This work was supported, in part, by the National Institute of Biomedical Imaging and Bioengineering through award number 1R01EB026510, the National Institute of General Medical Sciences through award number T32GM008152 (to H. Ardehali), the National Cancer Institute through award number F30CA203325, the NU Flow Cytometry Core Facility supported by a Cancer Center Support Grant (NCI 5P30CA060553), the NUSeq Core of the Northwestern Center for Genetic Medicine, an NU Chemistry of Life Processes Chicago Area Undergraduate Research Symposium award (to V.K.), and an NU Undergraduate Research Grant (to M.H.).
ASJC Scopus subject areas
- General