Gabriel Sigrist
A5079424896- SARS-CoV-2 and COVID-19 Research
- RNA Interference and Gene Delivery
- Viral Infections and Immunology Research
- PI3K/AKT/mTOR signaling in cancer
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Glycosylation and Glycoproteins Research
- PARP inhibition in cancer therapy
- Advanced biosensing and bioanalysis techniques
Molecular Partners (Switzerland)
2017-2022
Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage three units spike protein trimer SARS-CoV-2 and inhibit ACE2 binding high potency, as revealed by cryo-electron microscopy analysis. cooperative together...
MP0250 is a multi-domain drug candidate currently being tested in clinical trials for the treatment of cancer. It comprises one anti-vascular endothelial growth factor-A (VEGF-A), anti-hepatocyte factor (HGF), and two anti-human serum albumin (HSA) DARPin® domains within single polypeptide chain. While there first validation single-domain candidate, little known about candidates comprising multiple domains. Here, we show that can be expressed at 15 g/L soluble form E. coli high cell-density...
Abstract Globally accessible therapeutics against SARS-CoV-2 are urgently needed. Here, we report the generation of first anti-SARS-CoV-2 DARPin molecules with therapeutic potential as well rapid large-scale production capabilities. Highly potent multivalent low picomolar virus neutralization efficacies were generated by molecular linkage three different monovalent molecules. These target various domains spike protein, thereby limiting possible viral escape. Cryo-EM analysis individual...
Abstract SARS-CoV-2 has infected millions of people globally and continues to undergo evolution. Emerging variants can be partially resistant vaccine induced immunity therapeutic antibodies, emphasizing the urgent need for accessible, broad-spectrum therapeutics. Here, we report a comprehensive study ensovibep, first trispecific clinical DARPin candidate, that simultaneously engage all three units spike protein trimer potently inhibit ACE2 interaction, as revealed by structural analyses. The...