Martin Fussenegger


Last Name

Fussenegger

First Name

Martin

ORCID

0000-0001-8545-667X

Organisational unit

03694 - Fussenegger, Martin / Fussenegger, Martin

Search Results

Publications1 - 10 of 151
  • Engineering precision therapies: lessons and motivations from the clinic
    Item type: Journal Article
    Xie, Mingqi; Viviani, Mirta; Fussenegger, Martin (2021)
    Synthetic Biology
  • Caspase Regulation at the Molecular Level
    Item type: Book Chapter
    Kaufmann, Hitto; Fussenegger, Martin (2004)
    Cell Engineering ~ Apoptosis
  • From synthetic biology to human therapy: engineered mammalian cells
    Item type: Review Article
    Scheller, Leo; Fussenegger, Martin (2019)
    Current Opinion in Biotechnology
  • Programming mammalian cell behaviors by physical cues
    Item type: Review Article
    Huang, Jinbo; Fussenegger, Martin (2025)
    Trends in Biotechnology
    In recent decades, the field of synthetic biology has witnessed remarkable progress, driving advances in both research and practical applications. One pivotal area of development involves the design of transgene switches capable of precisely regulating specified outputs and controlling cell behaviors in response to physical cues, which encompass light, magnetic fields, temperature, mechanical forces, ultrasound, and electricity. In this review, we delve into the cutting-edge progress made in the field of physically controlled protein expression in engineered mammalian cells, exploring the diverse genetic tools and synthetic strategies available for engineering targeting cells to sense these physical cues and generate the desired outputs accordingly. We discuss the precision and efficiency limitations inherent in these tools, while also highlighting their immense potential for therapeutic applications.
  • Toward a world of electrogenetics
    Item type: Presentation
    Fussenegger, Martin (2024)
  • Engineering receptors in the secretory pathway for orthogonal signalling control
    Item type: Journal Article
    Mahameed, Mohamed; Wang, Pengli; Xue, Shuai; et al. (2022)
    Nature Communications
    Synthetic receptors targeted to the secretory pathway often fail to exhibit the expected activity due to post-translational modifications (PTMs) and/or improper folding. Here, we engineered synthetic receptors that reside in the cytoplasm, inside the endoplasmic reticulum (ER), or on the plasma membrane through orientation adjustment of the receptor parts and by elimination of dysfunctional PTMs sites. The cytoplasmic receptors consist of split-TEVp domains that reconstitute an active protease through chemically-induced dimerization (CID) that is triggered by rapamycin, abscisic acid, or gibberellin. Inside the ER, however, some of these receptors were non-functional, but their activity was restored by mutagenesis of cysteine and asparagine, residues that are typically associated with PTMs. Finally, we engineered orthogonal chemically activated cell-surface receptors (OCARs) consisting of the Notch1 transmembrane domain fused to cytoplasmic tTA and extracellular CID domains. Mutagenesis of cysteine residues in CID domains afforded functional OCARs which enabled fine-tuning of orthogonal signalling in mammalian cells.
  • At the crossroads of biology and electronics
    Item type: Review Article
    Unal, Gokberk; Fussenegger, Martin (2025)
    Current Opinion in Biotechnology
    All cells are innately equipped with systems to detect and respond to electrical inputs in the form of reactive oxygen species, redox signaling, or membrane depolarization through ion exchange. Electrogenetics aims to leverage these cellular systems to create interfaces between biology and electronics, in order to achieve levels of precision in spatiotemporal control of gene and protein expression that are not possible with chemo-, opto-, or thermogenetics. In this review, we discuss the impact, challenges, and prospects of electrogenetics in the context of recent cutting-edge applications.
  • Designing cell-based treatment strategies of the future
    Item type: Presentation
    Fussenegger, Martin (2020)
  • Rational design and optimization of synthetic gene switches for controlling cell-fate decisions in pluripotent stem cells
    Item type: Journal Article
    Haellman, Viktor; Saxena, Pratik; Jianga, Yanrui; et al. (2021)
    Metabolic Engineering
    Advances in synthetic biology have enabled robust control of cell behavior by using tunable genetic circuits to regulate gene expression in a ligand-dependent manner. Such circuits can be used to direct the differentiation of pluripotent stem cells (PSCs) towards desired cell types, but rational design of synthetic gene circuits in PSCs is challenging due to the variable intracellular environment. Here, we provide a framework for implementing synthetic gene switches in PSCs based on combinations of tunable transcriptional, structural, and posttranslational elements that can be engineered as required, using the vanillic acid-controlled transcriptional activator (VanA) as a model system. We further show that the VanA system can be multiplexed with the well-established reverse tetracycline-controlled transcriptional activator (rtTA) system to enable independent control of the expression of different transcription factors in human induced PSCs in order to enhance lineage specification towards early pancreatic progenitors. This work represents a first step towards standardizing the design and construction of synthetic gene switches for building robust gene-regulatory networks to guide stem cell differentiation towards a desired cell fate.
  • Multi-gene engineering: simultaneaous espresson and knockdown of six genes off a single platform
    Item type: Journal Article
    Greber, David; Fussenegger, Martin (2007)
    Biotechnology and Bioengineering
    Increases in our understanding of gene function have greatly expanded the repertoire of possible genetic interventions at our disposal with the consequence that many genetic engineering applications require multiple manipulations in which target genes can be both overexpressed and silenced in a simple and co-ordinated manner. Using synthetic introns as a source of encoding short-interfering RNA (siRNA), we demonstrate that it is possible to simultaneously express both a transgene and siRNA from a single polymerase (Pol) II promoter. By encoding siRNA as an intron between two protein domains requiring successful splicing for functionality, it was possible to demonstrate that splicing was occurring, that the coding genes (exonic transgenes) resulted in functional protein, and that the spliced siRNA-containing lariat was capable of modulating expression of a separate target gene. We subsequently extended this concept to develop pTRIDENT-based multi-cistronic vectors that were capable of co-ordinated expression of up to three siRNAs and three transgenes off a single genetic platform. Such multi-gene engineering technology, enabling concomitant transgene overexpression and target gene knockdown, should be useful for therapeutic, biopharmaceutical production, and basic research applications. Biotechnol.
Publications1 - 10 of 151