A5062136919- HER2/EGFR in Cancer Research
- Lung Cancer Treatments and Mutations
- Chronic Lymphocytic Leukemia Research
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- RNA regulation and disease
- RNA Interference and Gene Delivery
- Advanced Breast Cancer Therapies
- Streptococcal Infections and Treatments
- Bacteriophages and microbial interactions
- Genomics and Phylogenetic Studies
- Cancer Research and Treatments
- Ubiquitin and proteasome pathways
- Genetics, Aging, and Longevity in Model Organisms
- Biochemical and Molecular Research
- Cancer Genomics and Diagnostics
- Insect symbiosis and bacterial influences
- Mosquito-borne diseases and control
- Monoclonal and Polyclonal Antibodies Research
Boehringer Ingelheim (Austria)
2024
Vienna Biocenter
2018-2023
Vienna BioCenter Core Facilities
2018-2023
Umeå University
2011-2020
Max Perutz Labs
2012-2020
University of Vienna
2012-2020
Helmholtz Centre for Infection Research
2013
National Institutes of Health
2013
Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide bacteria and archaea with adaptive immunity against viruses plasmids by using CRISPR RNAs (crRNAs) to guide the silencing of invading nucleic acids. We show here that in a subset these systems, mature crRNA is base-paired trans-activating (tracrRNA) forms two-RNA structure directs CRISPR-associated protein Cas9 introduce double-stranded (ds) breaks target DNA. At sites complementary...
CRISPR-Cas is a rapidly evolving RNA-mediated adaptive immune system that protects bacteria and archaea against mobile genetic elements. The relies on the activity of short mature CRISPR RNAs (crRNAs) guide Cas protein(s) to silence invading nucleic acids. A set CRISPR-Cas, type II, requires trans-activating small RNA, tracrRNA, for maturation precursor crRNA (pre-crRNA) interference with sequences. Following co-processing tracrRNA pre-crRNA by RNase III, dual-tracrRNA:crRNA guides...
Abstract The CRISPR-Cas-derived RNA-guided Cas9 endonuclease is the key element of an emerging promising technology for genome engineering in a broad range cells and organisms. DNA-targeting mechanism type II CRISPR-Cas system involves maturation tracrRNA:crRNA duplex (dual-RNA), which directs to cleave invading DNA sequence-specific manner, dependent on presence Protospacer Adjacent Motif (PAM) target. We show that evolution dual-RNA bacteria produced remarkable sequence diversity. selected...
Abstract Mutations in ERBB2 (encoding HER2) occur 2% to 4% of non–small cell lung cancer (NSCLC) and confer poor prognosis. ERBB-targeting tyrosine kinase inhibitors, approved for treating other HER2-dependent cancers, are ineffective HER2-mutant NSCLC due dose-limiting toxicities or suboptimal potency. We report the discovery zongertinib (BI 1810631), a covalent HER2 inhibitor. Zongertinib potently selectively blocks HER2, while sparing EGFR, inhibits growth cells dependent on oncogenic...
<p>PRISM screen raw data.</p>
<div>Abstract<p>Mutations in <i>ERBB2</i> (encoding HER2) occur 2% to 4% of non–small cell lung cancer (NSCLC) and confer poor prognosis. ERBB-targeting tyrosine kinase inhibitors, approved for treating other HER2-dependent cancers, are ineffective HER2-mutant NSCLC due dose-limiting toxicities or suboptimal potency. We report the discovery zongertinib (BI 1810631), a covalent HER2 inhibitor. Zongertinib potently selectively blocks HER2, while sparing EGFR, inhibits...
<p>High-throughput zongertinib PRISM drug sensitivity screen and biomarker analysis.</p>
<p>High-throughput PRISM drug sensitivity screen in cancer cell lines.</p>
<p>Tempus data analysis results.</p>
<p>In vitro biomarker modulation of (phospho-)protein and mRNA levels post poziotinib or zongertinib treatment.</p>
<p>Graphical NMR spectra of zongertinib and BI-3999</p>
<p>MANO method and results. Sheet 1: Primer sequence for the bar code amplification. 2: next-generation sequencing analysis. 3: Raw data zongertinib (BI 1810631 in table) drug sensitivity assay.</p>
<p>In vivo tumor responses for zongertinib monotherapy or combinations.</p>
<p>Tolerability data for zongertinib in mouse xenotransplantation assays.</p>
<p>Synthesis and in vivo DMPK profile of zongertinib</p>
Abstract CRISPR-Cas9 is an efficient and versatile tool for genome engineering in many species. However, inducible editing systems that regulate Cas9 activity or sgRNA expression often suffer from significant limitations, including reduced capacity, off-target effects, leaky expression. Here, we develop a precisely controlled cassette can be combined with widely-used Cre systems, termed CRISPR-Switch (SgRNA With Induction/Termination by Homologous recombination). Switch-ON facilitates...
Streptococcus pyogenes Cas9 (SpCas9) and derived enzymes are widely used as genome editors, but their promiscuous nuclease activity often induces undesired mutations chromosomal rearrangements. Several strategies for mapping off-target effects have emerged, they suffer from limited sensitivity. To increase the detection sensitivity, we develop an assessment workflow that uses Duplex Sequencing. The strategy increases sensitivity by one order of magnitude, identifying previously unknown...
Streptococcus pyogenes is a human pathogen responsible for wide spectrum of diseases ranging from mild to life-threatening infections. During the infectious process, temporal and spatial expression pathogenicity factors tightly controlled by complex network protein RNA regulators acting in response various environmental signals. Here, we focus on class small (sRNAs) present first complete analysis sRNA sequencing data S. pyogenes. In SF370 clinical isolate (M1 serotype), identified 197 428...