Synthetic Biology for Novel Immunotherapies - NCCR MSE

Synthetic Biology for Novel Immunotherapies

Synthetic Biological Circuits.
Synthetic Biological Circuits.

The project is dedicated to rational design and engineering of mammalian cells augmented with complex functionalities, for applications in non-medical biotechnology.

The two application areas include rational forward design of bioproducing mammalian cell lines, and the development of sentinel (reporter) cells for highly-informative drug discovery assays. In the former, we combine the laters tools of genetic engineering such as synthetic biology and automation, with the recent genome editing approaches and rational in situ control of the bioproduction process on a single cell level, to achieve end-to-end workflow for biomanufacturing cells without the need for screening. In the latter project, we harness the power of biomolecular computing to engineerer reporter cells that detect multiple drug effects in parallel. This dramatically increases the information content of a cell-based drug screening assay without reducing the throughput.


J. Doshi, K. Willis, A. Madurga, C. Stelzer, Y. Benenson “Multiple Alternative Promoters and Alternative Splicing Enable Universal Transcription-Based Logic Computation in Mammalian Cells“ Cell Rep. 2020. [DOI]
S. Höllerer, L. Papaxanthos, A. C. Gumpinger, K. Fischer, C. Beisel, K. Borgwardt, Y. Benenson, M. Jeschek “Large-Scale DNA-Based Phenotypic Recording and Deep Learning Enable Highly Accurate Sequence-Function Mapping“ Nat. Commun. 2020. [DOI]
A. Mazé, Y. Benenson “Artificial signaling in mammalian cells enabled by prokaryotic two-component system“ Nat. Chem. Biol. 2019. [DOI]
M. Dastor, J. Schreiber, L. Prochazka, B. Angelici, J. Kleinert, I. Klebba, J. Doshi, L. Shen, Y. Benenson “A Workflow for In Vivo Evaluation of Candidate Inputs and Outputs for Cell Classifier Gene Circuits“ ACS Synth. Biol. 2017. [DOI]
L. Prochazka, Y. Benenson, P. W. Zandstra “Synthetic gene circuits and cellular decision-making in human pluripotent stem cells“ Curr. Opin. Syst. Biol. 2017. [DOI]
P. Mohammadi, N. Beerenwinkel, Y. Benenson “Automated Design of Synthetic Cell Classifier Circuits Using a Two-Step Optimization Strategy“ 2017. [DOI]
J. Schreiber, M. Arter, N. Lapique, B. Haefliger, Y. Benenson “Model‐guided combinatorial optimization of complex synthetic gene networks“ Mol. Syst. Biol. 2016, 12:899. [DOI]
Y. Benenson “Complexity from Simple Building Blocks: Engineering Large-scale Information-processing Networks from Molecules“ Chimia 2016, 6:392. [DOI]
B. Häfliger, L. Prochazka, B. Angelici, Y. Benenson “Precision multidimensional assay for high-throughput microRNA drug discovery“ Nat. Commun. 2016, 7:DOI: 10.1038/ncomms10709. [DOI] [More Information]

Project Leader

Yaakov Benenson


Benenson group @D-BSSE