A5015813819- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- MicroRNA in disease regulation
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Bacteriophages and microbial interactions
- Polyamine Metabolism and Applications
- Genetics, Aging, and Longevity in Model Organisms
- RNA modifications and cancer
- HIV/AIDS drug development and treatment
- Protein Degradation and Inhibitors
- Plant Virus Research Studies
- Cancer Mechanisms and Therapy
- Quinazolinone synthesis and applications
- Computational Drug Discovery Methods
- Advanced Breast Cancer Therapies
- Synthesis and Biological Evaluation
- Pneumocystis jirovecii pneumonia detection and treatment
- Radioactive element chemistry and processing
- Phenothiazines and Benzothiazines Synthesis and Activities
- Ubiquitin and proteasome pathways
- Immune Cell Function and Interaction
- Histone Deacetylase Inhibitors Research
- Analytical chemistry methods development
ETH Zurich
2012-2025
AstraZeneca (United Kingdom)
2018-2023
University of Cambridge
2009-2016
École Polytechnique Fédérale de Lausanne
2015
Wellcome Trust
2009-2011
The Gurdon Institute
2009-2011
Granta Design (United Kingdom)
2008
Background: Despite tremendous advances in antiretroviral therapy (ART) against HIV-1 infections, no cure or vaccination is available. Therefore, discovering novel therapeutic strategies remains an urgent need. In that sense, miRNAs and miRNA therapeutics have moved intensively into the focus of recent HIV-1-related investigations. A strong reciprocal interdependence has been demonstrated between infection changes intrinsic cellular milieu. This interrelationship may direct potential...
Stereochemically-pure 2'-O-(2-methoxyethyl)-phosphorothioate (PS-MOE) oligonucleotides were synthesized from new chiral oxazaphospholidine-containing nucleosides. Thermal stability studies showed that the incorporation of Rp-PS linkages increased RNA-binding affinity. In cells, a full Rp-PS-MOE splice-switching oligonucleotide targeting part ferrochelatase gene was more potent than its Sp-PS counterpart, but similar potency to stereorandom PS-parent sequence.
Several recent studies have provided evidence that LIN28, a cytoplasmic RNA-binding protein, inhibits the biogenesis of members let-7 microRNA family at Dicer step in both mammals and Caenorhabditis elegans. However, precise mechanism inhibition is still poorly understood. Here we report on an vitro study, which combined RNase footprinting, gel shift binding assays, processing to investigate molecular basis function interaction between native let-7g precursor (pre-let-7g) LIN28. We mapped...
Small molecules enhance Dicer processing of a let-7 miRNA precursor through antagonization the Lin28–pre-let-7 interaction.
Oligonucleotide delivery in vivo is commonly seen as the principal hurdle to successful development of oligonucleotide drugs. In an analysis 26 drugs recently evaluated late-stage clinical trials we found that date at least half have demonstrated suppression target mRNA and/or protein levels relevant cell types man, including those present liver, muscle, bone marrow, lung, blood and solid tumors. Overall, this strongly implies are being delivered appropriate disease tissues. Strikingly also...
The development of small molecule kinase drugs is a rapidly evolving field and represents one the most important research areas within oncology. This innovation letter provides an overview analysis approved according to their WHO registration (INN) dates, primary biological targets, selectivity structural similarities, which are also depicted in associated poster. It discusses new trends drug discovery programs such as novel mechanisms action, diverse indications.
G-quadruplexes are naturally-occurring structures found in RNAs and DNAs. Regular RNA highly stable due to stacked planar arrangements connected by short loops. However, reports of irregular quadruplex increasing recent genome-wide studies suggest that they influence gene expression. We have investigated a grouping G2-motifs the UTRs eight genes involved polyamine biosynthesis, concluded several likely form novel metastable G-quadruplexes. performed comprehensive biophysical characterization...
In animals, microRNAs frequently form families with related sequences. The functional relevance of miRNA and the relative contribution family members to target repression have remained, however, largely unexplored. Here, we used Caenorhabditis elegans miR-58 family, composed primarily four highly abundant miR-58.1, miR-80, miR-81, miR-82, as a model investigate redundancy their impact on expression in an vivo setting. We found that repress overlapping sets targets predominantly additive...
Abstract When used as inhibitors of gene expression in vivo, oligonucleotides require modification their structures to boost binding affinity for complementary target RNAs. To date, hundreds modifications have been designed and tested but few proven be useful. Among those investigated are mono‐ polyamino‐groups. These positively charged at physiological pH appended an effort reduce electrostatic repulsion during hybridization RNAs, generally shown relatively minor benefits binding. We...
Large compound libraries utilised for HTS often include metal contaminated compounds which can interfere with assay signal or target biology, and therefore appear as hits. Pursuit of these divert considerable time resource away from more propitious hits, yet there is currently no established method detecting impurities in a rapid effective manner. Here we describe the development application high-throughput to identify contaminants using acoustic mist ionisation mass spectrometry (AMI-MS)....
RNA G-quadruplexes are secondary structures that implicated in many cellular processes. Although conventional biophysical techniques widely used for their vitro characterization, more advanced methods needed to study complex equilibria and the kinetics of folding. We have developed a new Förster resonance energy-transfer-based method detect folding G-quadruplexes, which is enabled by labeling 2'-positions participating guanosines with fluorophores. Importantly, this does not interfere...
Abstract Background Despite tremendous advances in antiretroviral therapy (ART) against HIV-1 infections no cure or vaccination is available. Therefore, discovering novel therapeutic strategies remains an urgent need. In that sense, miRNAs and miRNA therapeutics have moved intensively into the focus of recent related investigations. A strong reciprocal interdependence has been demonstrated between infection changes intrinsic cellular milieu. This interrelationship may direct potential...
The World Health Organization (WHO) publishes quarterly reports listing Internationally recognized Non-proprietary Names (INNs) for substances that are to be marketed as a pharmaceutical. Each INN is also globally the unique generic name of drug. contains specific suffix defines what compound class drug belongs to. This poster depicts chemical structures, biological targets, most advanced indications and associated pharmaceutical companies small molecule compounds with “-nib” which refers...