Model-guided design of mammalian genetic programs

J. J. Muldoon, V. Kandula, M. Hong, P. S. Donahue, J. D. Boucher, N. Bagheri, J. N. Leonard*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 languageEnglish (US)
Article numbereabe9375
JournalScience Advances
Volume7
Issue number8
DOIs
StatePublished - Feb 19 2021

ASJC Scopus subject areas

  • General

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