A5032337906- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- RNA and protein synthesis mechanisms
- Microbial Inactivation Methods
- Transgenic Plants and Applications
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Immune cells in cancer
- Mesenchymal stem cell research
- MicroRNA in disease regulation
- Advanced biosensing and bioanalysis techniques
- Mosquito-borne diseases and control
- interferon and immune responses
- Viral Infections and Immunology Research
- RNA modifications and cancer
- RNA Research and Splicing
- Angiogenesis and VEGF in Cancer
- Nanoplatforms for cancer theranostics
- Cancer Research and Treatments
- Viral Infections and Vectors
- Viral gastroenteritis research and epidemiology
- Circular RNAs in diseases
- SARS-CoV-2 and COVID-19 Research
- Virology and Viral Diseases
Ghent University
2015-2022
Cancer Research Institute Ghent
2018-2021
Self-amplifying RNA vaccines may induce equivalent or more potent immune responses at lower doses compared to non-replicating mRNA via amplified antigen expression. In this paper, we demonstrate that 1 μg of an LNP-formulated dual-antigen self-amplifying vaccine (ZIP1642), encoding both the S-RBD and N antigen, elicits considerably higher neutralizing antibody titers against Wuhan-like Beta B.1.351 Delta B.1.617.2 SARS-CoV-2 variants those convalescent patients. addition, ZIP1642 vaccination...
In this work, we studied the expression kinetics and innate immune response of a self-amplifying mRNA (sa-RNA) after electroporation lipid-nanoparticle (LNP)-mediated delivery in skin mice. Intradermal sa-RNA resulted plateau-shaped expression, with plateau between day 3 10. The overall protein was significantly higher than that obtained plasmid DNA (pDNA) or non-replication mRNAs. Moreover, using IFN-β reporter mice, elucidated intradermal induced short-lived moderate response, which did...
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 self-replicating mRNA (sr-mRNA) vaccine the pre-membrane envelope (prM-E) glycoproteins ZIKV. Intradermal electroporation few 1 µg mRNA-based ZIKV induced potent humoral cellular immune responses in BALB/c especially IFNAR1-/- C57BL/6 mice, resulting complete...
Recently, secreted microRNAs (miRNAs) have received a lot of attention since they may act as autocrine factors. However, how miRNAs influence embryonic development is still poorly understood. We identified 294 miRNAs, 114 known, and 180 novel, in the conditioned medium individually cultured bovine embryos. Of these miR-30c miR-10b were much more abundant slow cleaving embryos compared to intermediate ones. MiR-10b, miR-novel-44, miR-novel-45 higher expressed degenerate blastocysts, while...
Synthetic mRNAs are an appealing platform with multiple biomedical applications ranging from protein replacement therapy to vaccination. In comparison conventional mRNA, synthetic self-amplifying (sa-mRNAs) gaining interest because of their higher and longer-lasting expression. However, sa-mRNAs also elicit innate immune response, which may complicate clinical application. Approaches reduce the immunity have not been studied in detail. Here we investigated, vivo, effect several inhibitors a...
Synthetic mRNA is becoming increasingly popular as an alternative to pDNA-based gene therapy. Currently, multiple synthetic platforms have been developed. In this study we investigated the expression kinetics and changes in encoding cytokine chemokine levels following intradermal electroporation pigs of pDNA, self-replicating mRNA, modified unmodified mRNA. The tended induce highest protein expression, followed by Interestingly, was able maintain its high during at least 12 days. contrast,...
Synthetic mRNA therapeutics have the potential to revolutionize healthcare, as they enable patients produce therapeutic proteins inside their own bodies. However, convenient methods that allow external control over timing and magnitude of protein production after in vivo delivery synthetic are lacking. In this study, we validate utility a self-amplifying (RNA replicon) whose expression can be turned off using genetic switch responds oral administration trimethoprim (TMP), US Food Drug...
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 therapeutic agents. Using in vivo imaging, the short-term accumulation systemically injected monocytes, macrophages and myeloid-derived suppressor (MDSCs) was compared mice bearing fat pad mammary carcinomas. Monocytes demonstrated almost identical ex distribution patterns maximal tumor-associated seen 48 hours...
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 sr-mRNA combination with a protein-based RNase inhibitor increased expression efficiency, success rate, and repeatability data. The should be added just before because storage together at -80°C resulted partial loss beneficial effect. Furthermore, location also had major effect on...
Tumor associated macrophages are an essential part of the tumor microenvironment. Consequently, bone marrow-derived monocytes (BMDMs) continuously recruited to tumors and therefore seen as ideal delivery vehicles with tumor-targeting properties. By using immune cell depleting agents macroscopic in vivo fluorescence imaging, we demonstrated that removal endogenous (but not neutrophils) leads increased accumulation exogenously administered BMDMs. means intravital microscopy (IVM), confirmed...
Abstract In this work we studied the expression kinetics and innate immune response of a self-amplifying mRNA (sa-RNA) after electroporation lipid nanoparticle (LNP) mediated delivery in skin mice. Intradermal sa-RNA resulted plateau-shaped with plateau between day 3 10. The overall protein was significant higher than that obtained pDNA or non-replication mRNAs. Moreover, intradermal induced short-lived did not affect sa-RNA. A complete different profile observed when LNPs were used. peaked...
Abstract Synthetic mRNAs are an appealing therapeutic platform with multiple biomedical applications ranging from protein replacement therapy to vaccination. In comparison conventional mRNA, synthetic self-amplifying (sa-mRNAs) gaining increased interest due their higher and longer-lasting expression. However, sa-mRNAs also elicit innate immune response, which may complicate the clinical translation of this platform. Approaches reduce immunity have not been studied in detail. work we...
Identifying microRNA (miRNA) differentially secreted by intermediate (cleaved between 26.6-31.4 hpi) and slow cleaving bovine embryos after 31.4 hpi), investigating how they influence embryo development consequently if can be used as biomarkers for development. MicroRNA collected from conditioned media (CM) of 167 individually cultured were sequenced on an Illumina Miseq (Illumina, San Diego, CA, USA) small RNA library construction with the Tailormix v2 kit (SeqMatic, Fremont, compared...