Novel Diagnostic and Therapeutic Opportunities by Engineering Molecular Systems into Cells - NCCR MSE

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.

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.

Publications

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