1. TXM peptides inhibit SARS-CoV-2 infection, syncytia formation, and lower inflamatory consequencesTea Govednik, Duško Lainšček, Urška Kuhar, Marva Lachish, Sandra Janežič, Malan Štrbenc, Uroš Krapež, Roman Jerala, Daphne Atlas, Mateja Manček Keber, 2024, original scientific article Abstract: After three years of the SARS-CoV-2 pandemic, the search and availability of relatively low-cost benchtop therapeutics for people not at high risk for a severe disease are still ongoing. Although vaccines and new SARS-CoV-2 variants reduce the death toll, the long COVID-19 along with neurologic symptoms can develop and persist even after a mild initial infection. Reinfections, which further increase the risk of sequelae in multiple organ systems as well as the risk of death, continue to require caution. The spike protein of SARS-CoV-2 is an important target for both vaccines and therapeutics. The presence of disulfide bonds in the receptor binding domain (RBD) of the spike protein is essential for its binding to the human ACE2 receptor and cell entry. Here, we demonstrate that thiol-reducing peptides based on the active site of oxidoreductase thioredoxin 1, called thioredoxin mimetic (TXM) peptides, can prevent syncytia formation, SARS-CoV-2 entry into cells, and infection in a mouse model. We also show that TXM peptides inhibit the redox-sensitive HIV pseudotyped viral cell entry. These results support disulfide targeting as a common therapeutic strategy for treating infections caused by viruses using redox-sensitive fusion. Furthermore, TXM peptides exert anti-inflammatory properties by lowering the activation of NF-κB and IRF signaling pathways, mitogen-activated protein kinases (MAPKs) and lipopolysaccharide (LPS)-induced cytokines in mice. The antioxidant and anti-inflammatory effects of the TXM peptides, which also cross the blood-brain barrier, in combination with prevention of viral infections, may provide a beneficial clinical strategy to lower viral infections and mitigate severe consequences of COVID-19. Keywords: SARS-CoV-2, Disulfides, Thiol-reacting compound, Spike, Anti-inflammatory activity Published in DiRROS: 06.02.2024; Views: 184; Downloads: 88 Full text (7,11 MB) This document has many files! More... |
2. Engineered combinatorial cell device for wound healing and bone regenerationLucija Kadunc, Duško Lainšček, Rok Gašperšič, Petra Sušjan, Uroš Kovačič, Miha Butinar, Boris Turk, Roman Jerala, Iva Hafner Bratkovič, 2023, original scientific article Abstract: Growth factors are the key regulators that promote tissue regeneration and healing processes. While the effects of individual growth factors are well documented, a combination of multiple secreted growth factors underlies stem cell–mediated regeneration. To avoid the potential dangers and laborintensive individual approach of stem cell therapy while maintaining their regeneration-promoting effects based on multiple secreted growth factors, we engineered a “mix-and-match” combinatorial platform based on a library of cell lines producing growth factors. Treatment with a combination of growth factors secreted by engineered mammalian cells was more efficient than with individual growth factors or even stem cell–conditioned medium in a gap closure assay. Furthermore, we implemented in a mouse model a device for allogenic cell therapy for an in situ production of growth factors, where it improved cutaneous wound healing. Augmented bone regeneration was achieved on calvarial bone defects in rats treated with a cell device secreting IGF, FGF, PDGF, TGF-β, and VEGF. In both in vivo models, the systemic concentration of secreted factors was negligible, demonstrating the local effect of the regeneration device. Finally, we introduced a genetic switch that enables temporal control over combinations of trophic factors released at different stages of regeneration mimicking the maturation of natural wound healing to improve therapy and prevent scar formation. Keywords: wound healing, bone regeneration, growth factors Published in DiRROS: 01.06.2023; Views: 498; Downloads: 194 Full text (2,59 MB) This document has many files! More... |
3. Selective inhibition of NLRP3 inflammasome by designed peptide originating from ASCPetra Sušjan, Duško Lainšček, Žiga Strmšek, Vesna Hodnik, Gregor Anderluh, Iva Hafner Bratkovič, 2020, original scientific article Keywords: blood-brain barrier, inflammation, ▫$IL-1beta$▫, peptide inhibitors Published in DiRROS: 24.03.2022; Views: 667; Downloads: 440 Full text (3,68 MB) This document has many files! More... |
4. Design of coiled-coil protein-origami cages that self-assemble in vitro and in vivoAjasja Ljubetič, Fabio Lapenta, Helena Gradišar, Igor Drobnak, Jana Aupič, Žiga Strmšek, Duško Lainšček, Iva Hafner Bratkovič, Andreja Majerle, Nuša Krivec, Mojca Benčina, Tomaž Pisanski, Tanja Ćirković-Veličković, Adam Round, José María Carazo, Roberto Melero, Roman Jerala, 2017, original scientific article Published in DiRROS: 17.04.2018; Views: 3884; Downloads: 2538 Full text (741,03 KB) This document has many files! More... |