Publications

This review summarises major highlights on the structural biology of the chlamydial envelope. Chlamydiae are obligate intracellular bacteria, characterised by a unique biphasic developmental cycle. Depending on the stage of their lifecycle, they appear in the form of elementary or reticulate bodies. Since these particles have distinctive functions, it is not surprising that their envelope differs in lipid as well as in protein content. Vice ...

Strategies that can reduce the harmful side effects of potent immunomodulatory drugs are in high demand to facilitate clinical translation of the newest generation of immunotherapy. Indeed, uncontrolled triggering of the immune system can lead to life-threatening cascade reactions, such as e.g. cytokine storm. In particular, drug formulations that combine simplicity and degradability are of formidable relevance. Imidazoquinolines are an ...

mRNA-lipoplex vaccines are currently being explored in phase II clinical trials for the treatment of patients with advanced solid tumors. Mechanistically, these mRNA-lipoplex vaccines are characterized by the induction of type I interferon (IFN) centered innate responses. Earlier studies have identified type I IFNs as major regulators of the T cell response instigated by mRNA-lipoplex vaccines. However, stimulatory or, in contrast, profound ...

Chlamydia are obligate intracellular bacteria, characterized by a unique biphasic developmental cycle. Specific interactions with the host cell are crucial for the bacteria's survival and amplification because of the reduced chlamydial genome. At the start of infection, pathogen-host interactions are set in place in order for Chlamydia to enter the host cell and reach the nutrient-rich peri-Golgi region. Once intracellular localization is ...

Local administration of naked self-replicating mRNA (sr-mRNA) in the skin or muscle using electroporation is effective but hampered by low repeatability. In this manuscript, we demonstrated that intradermal electroporation of sr-mRNA in combination with a protein-based RNase inhibitor increased the expression efficiency, success rate, and repeatability of the data. The RNase inhibitor should be added just before administration because storage of ...

To combat emerging infectious diseases like Zika virus (ZIKV), synthetic messenger RNAs (mRNAs) encoding viral antigens are very attractive as they allow a rapid, generic, and flexible production of vaccines. In this work, we engineered a self-replicating mRNA (sr-mRNA) vaccine encoding the pre-membrane and envelope (prM-E) glycoproteins of ZIKV. Intradermal electroporation of as few as 1 µg of this mRNA-based ZIKV vaccine induced potent humoral ...

Synthetic mRNA is an attractive vehicle for gene therapies because of its transient nature and improved safety profile over DNA. However, unlike DNA, broadly applicable methods to control expression from mRNA are lacking. Here we describe a platform for small-molecule-based regulation of expression from modified RNA (modRNA) and self-replicating RNA (replicon) delivered to mammalian cells. Specifically, we engineer small-molecule-responsive RNA ...

Solid tumors frequently coexist with a degree of local chronic inflammation. Recruited myeloid cells can therefore be considered as interesting vehicles for tumor-targeted delivery of therapeutic agents. Using in vivo imaging, the short-term accumulation of systemically injected monocytes, macrophages and myeloid-derived suppressor cells (MDSCs) was compared in mice bearing fat pad mammary carcinomas. Monocytes and macrophages demonstrated ...

Localized therapeutic modalities that subvert the tumor microenvironment from immune-suppressive to pro-immunogenic can elicit systemic antitumor immune responses that induce regression of directly treated as well as nontreated distal tumors. A key toward generating robust antitumor T cell responses is the activation of dendritic cells (DCs) in the tumor microenvironment. Treatment with agonists triggering various pattern recognition receptors ...