Novel Diagnostic and Therapeutic Opportunities by Engineering Molecular Systems into Cells

Novel Diagnostic and Therapeutic Opportunities by Engineering Molecular Systems into Cells

Anti-obesity designer implant. The implanted designer cells monitor the blood-fat levels of obese animals and coordinate expression of an appetite-suppressing peptide hormone which tells the animal that it is full. Consequently, food intake drops and body weight decreases until the animal reaches its normal body weight.
Anti-obesity designer implant. The implanted designer cells monitor the blood-fat levels of obese animals and coordinate expression of an appetite-suppressing peptide hormone which tells the animal that it is full. Consequently, food intake drops and body weight decreases until the animal reaches its normal body weight.

Benefitting from synergies and the unique expertise of various projects within the NCCR Molecular Systems Engineering, the focus will be on the design of cellular diagnosis and therapeutic production factories that detect and correct physiological disorders.

In modern medicine, diagnosis of disorders kick-off therapeutic interventions and early-stage discovery of pathologies significantly improves therapeutic success. However, most disorders will only be diagnosed when discomfort urges a patient to seek medical advice. In these cases treatment may be too late.

Tumour markers, immune response proteins and pathology-associated metabolites are monitored for diagnosis and therapy management by quantitative analysis of blood samples or biopsies. This requires medical intervention that is typically initiated when the patient has symptoms and is seeking medical advice. However, preventive medical check-ups for the prognosis of physiological disorders are not receiving enough attention.

Synthetic gene circuits that constantly monitor physiological processes, detect a pathological situation and produce diagnostic output or coordinate therapeutic interventions could change our health-care system from the standard symptom-treatment scheme to a symptom-free preventive care strategy.

Read what various media reported in March/April 2015 on a scientific paper (see "Articles" below"): NZZ (CH), ETH News (CH), Le Temps (CH), Stern (D) and stand-up comedian Bill Maher (USA). Earlier, Sonntagsblick wrote about "Implantat für den Insulin Haushalt" (15.2.2015) and Basler Zeitung about "Mit Gedanken lassen sich Mäuse lenken" (12.11.2014).


Scientific Highlight

Mind-Controlled Gene Expression (read the publication in full here): The Fussenegger-Group has designed a synthetic mind-controlled gene switch that enables human brain activities and mental states to wirelessly program transgene expression in cells. This device harnesses the electric energy of a person’s brainwaves thanks to an electro-encephalogram to trigger a light-emitting diode, which remotely activates light-inducible genes (optogenetic switch) in a small implant placed in mice. This technolgy, which was selected by the Scientist as one of 2014’s “Big-Advance” in Science, may provide cell-based treatments that respond to specific mental states.


D. Bojar, M. FusseneggerProgramming mammalian gene expression with the antibiotic simocyclinone D8 and the flavonoid luteolin“ AIChE J. (2018). [Link]
Y. Liu, P. Bai, A. Woischnig, G. Charpin-El Hamri, H. Ye, M. Folcher, M. Xie, N. Khanna, M. FusseneggerImmunomimetic Designer Cells Protect Mice from MRSA Infection“ Cell (2018). [Link]
D. Bojar, L. Scheller, G. C. Hamri, M. Xie, M. FusseneggerCaffeine-inducible gene switches controlling experimental diabetes“ Nat. Commun. (2018). [Link]
M. Xie, M. FusseneggerDesigning cell function: assembly of synthetic gene circuits for cell biology applications“ Nat. Rev. Mol. Cell Biol. (2018). [Link]
Y. Okamoto, R. Kojima, F. Schwizer, E. Bartolami, T. Heinisch, S. MatileM. FusseneggerT. R. WardA cell-penetrating artificial metalloenzyme regulates a gene switch in a designer mammalian cell“ Nat. Commun. (2018). [Link]
R. Kojima, M. FusseneggerEngineering Whole Mammalian Cells for Target‐Cell‐Specific Invasion/Fusion“ Adv. Sci. (2018). [Link]
L. Scheller, T. Strittmatter, D. Fuchs, D. Bojar, M. FusseneggerGeneralized extracellular molecule sensor platform for programming cellular behavior“ Nat. Chem. Biol. (2018). [Link]
A. Tastanova, M. Folcher, M. Müller, G. Camenisch, A. Ponti, T. Horn, M. S. Tikhomirova, M. FusseneggerSynthetic biology-based cellular biomedical tattoo for detection of hypercalcemia associated with cancer“ Sci. Transl. Med. (2018). [Link]
R. Kojima, D. Bojar, G. Rizzi, G. C. Hamri, M. D. El-Baba, P. Saxena, S. Ausländer, K. R. Tan, M. FusseneggerDesigner exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment“ Nat. Commun. (2018). [Link]
H. Wang, M. Xie, G. Charpin-El Hamri, H. Ye, M. FusseneggerTreatment of chronic pain by designer cells controlled by spearmint aromatherapy“ Nat. Biomed. Eng. (2018). [Link]
S. Ausländer, X. Pierrat, L. Hellmann, L. Rachid, M. FusseneggerProgrammable full-adder computations in communicating three-dimensional cell cultures“ Nat. Methods (2017). [Link]
R. Kojima, L. Scheller, M. FusseneggerNonimmune cells equipped with T-cell-receptor-like signaling for cancer cell ablation“ Nat. Chem. Biol. (2017). [Link]
H. Chassin, B. Geering, L. Schukur, D. Ausländer, B. Lang, M. FusseneggerSensing and responding to allergic response cytokines through a genetically encoded circuit“ Nat. Commun. (2017). [Link]
V. Haellman, M. FusseneggerSynthetic biology – Engineering cell-based biomedical devices“ Curr. Opin. Biomed. Eng. (2017). [Link]
F. Sedlmayer, T. Jaeger, U. Jenal, M. FusseneggerQuorum-Quenching Human Designer Cells for Closed-Loop Control of Pseudomonas aeruginosa Biofilms“ Nano Lett. (2017). [Link]
P. Saxena, D. Bojar, H. Zulewski, M. FusseneggerGeneration of glucose-sensitive insulin-secreting beta-like cells from human embryonic stem cells by incorporating a synthetic lineage-control network“ J. Biotechnol. (2017). [Link]
M. Xie, D. Aubel, M. FusseneggerClosed-loop control systems – The quest for precision therapies for diabetes“ Curr. Opin. Syst. Biol. (2017). [Link]
A. P. Teixeira, M. FusseneggerSynthetic biology-inspired therapies for metabolic diseases“ Curr. Opin. Biotechnol. (2017). [Link]
D. Ausländer, M. FusseneggerSynthetic Biology‐The Synthesis of Biology“ Angew. Chem. Int. Ed. 56, 6396-419 (2017). [Link]
S. Ausländer, M. FusseneggerSynthetic RNA-based switches for mammalian gene expression control“ Curr. Opin. Biotechnol. 48, 54-60 (2017). [Link]
M. Muller, D. Auslander, A. Spinnler, J. Sikorski, M. Folcher, M. FusseneggerDesigned cell consortia as fragrance-programmable analog-to-digital converters“  13, 309-16 (2017). [Link]
M. Xie, H. Ye, H. Wang, G. Charpin-El Hamri, C. Lormeau, P. Saxena, J. StellingM. Fusseneggerβ-cell–mimetic designer cells provide closed-loop glycemic control“ Science 354, 1296-1301 (2016). [Link]
R. Kojima, D. Aubel, M. FusseneggerToward a world of theranostic medication: Programming biological sentinel systems for therapeutic intervention“ Adv. Drug Delivery Rev. 105, 66-76 (2016). [Link]
M. Xie, V. Haellman, M. FusseneggerV. HällmanSynthetic biology-application-oriented cell engineering.“ Curr. Opin. Biotechnol. 40, 139 (2016). [Link]
P. Saxena, B. C. Heng, P. Bai, M. Folcher, H. Zulewski, M. FusseneggerA programmable synthetic lineage-control network that differentiates human IPSCs into glucose-sensitive insulin-secreting beta-like cells“ Nat. Commun. 7, DOI:10.1038/ncomms11247 (2016). [Link] [More Information]
P. Bai, H. Ye, M. Xie, P. Saxena, H. Zulewski, G. Charpin-El Hamri, V. Djonov, M. FusseneggerA synthetic biology-based device prevents liver injury in mice“ J. Hepatol. 65, 84 (2016). [Link]
D. Auslaender, D. W. Fuchs, S. Huerlemann, M. FusseneggerEngineering a ribozyme cleavage-induced split fluorescent aptamer complementation assay“ Nucleic Acids Res. 44, e94 (2016). [Link]
A. Tastanova, A. Schulz, A. Tolstrup, A. Puklowski, H. Kaufmann, M. FusseneggerOverexpression of YY1 increases the protein production in mammalian cells“ J. Biotechnol. 219, 72 (2016). [Link]
P. Saxena, G. Charpin-El Hamri, M. Folcher, H. Zulewski, M. FusseneggerSynthetic gene network restoring endogenous pituitary-thyroid feedback control in experimental Graves' disease“ Proc. Natl. Acad. Sci. U.S.A. 113, 1244 (2016). [Link]
B. Geering, Z. Zokouri, S. Hurlemann, B. Gerrits, D. Auslander, A. Britschgi, M. P. Tschan, H. U. Simon, M. FusseneggerIdentification of Novel Death-Associated Protein Kinase 2 Interaction Partners by Proteomic Screening Coupled with Bimolecular Fluorescence Complementation“ Mol. Cell. Biol. 36, 132-43 (2016). [Link]
L. Lina Schukur, B. Geering, G. Charpin-El Hamri, M. FusseneggerImplantable synthetic cytokine converter cells with AND-gate logic treat experimental psoriasis“ Sci. Transl. Med. 7, DOI: 10.1126/scitranslmed.aac4964 (2015). [Link]
B. C. Heng, D. Aubel, M. FusseneggerProsthetic gene networks as an alternative to standard pharmacotherapies for metabolic disorders“ Curr. Opin. Biotechnol. 35, 37-45 (2015). [Link]
L. Schukur, B. Geering, M. FusseneggerHuman whole-blood culture system for ex vivo characterization of designer-cell function“ Biotechnol. Bioeng. 113, 588 (2015). [Link]
V. Haellman, M. FusseneggerV. HällmanSynthetic Biology-Toward Therapeutic Solutions“ J. Mol. Biol. 428, 945 (2015). [Link]
H. Wang, H. Ye, M. Xie, M. Daoud El-Baba, M. FusseneggerCosmetics-triggered percutaneous remote control of transgene expression in mice“ Nucleic Acids Res. 43, e91 (2015). [Link]
R. Kojima, D. Aubel, M. FusseneggerNovel theranostic agents for next-generation personalized medicine: small molecules, nanoparticles, and engineered mammalian cells“ Curr. Opin. Chem. Biol. 28, 29 (2015). [Link]
M. Xie, M. FusseneggerMammalian designer cells: Engineering principles and biomedical applications.“ Biotechnol. J. 10, 1005 (2015). [Link]
T. Kim, M. Folcher, M. Doaud-El Baba, M. FusseneggerA Synthetic Erectile Optogenetic Stimulator Enabling Blue-Light-Inducible Penile Erection“ Angew. Chem. Int. Ed. 54, 5933 (2015). [Link] [More Information]
T. Kim, M. Folcher, G. Charpin-El Hamri, M. FusseneggerA synthetic cGMP-sensitive gene switch providing Viagra((R))-controlled gene expression in mammalian cells and mice“ Metab. Eng. 29, 169-79 (2015). [Link]
B. Geering, M. FusseneggerSynthetic immunology: modulating the human immune system“ Trends Biotechnol. 33, 65-79 (2015). [Link]

Project Leader

Martin Fussenegger


The therapeutic designer cells will be developed and tested in collaboration with projects led by Daniel Müller, Gebhard Schertler, Janos Vörös, Savas Tay, Thomas R. Ward, Wolfgang Meier, Sven Panke, Botond Roska, and Yaakov Benenson.


Read more about the Fussenegger-Group here.