CHIMIA
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Portable and Handheld Raman Instruments Open a Multitude of Applications
Full text linkFundamental science can sometimes take a long time until it is useful for practical applications, as was the case for Raman spectroscopy. For a long time, it lacked powerful excitation sources and sensitive detectors. However as technology evolved, the number of exciting applications has boomed. Modern Raman spectroscopy has significant advantages, especially in sample preparation. Handheld Raman devices can be very compact and therefore be easily taken to the sample instead of bringing the sample to the lab. Non-destructive measurements obviously are important in gemmology and mineralogy, even in space. In the field of archaeology, pigments in precious ancient paintings, scrolls or books can be identified. This application is also used to identify fraud and falsification and in studies from a medical school they have reported that Raman spectroscopy can be applied to distinguish cancerous tissue from healthy tissue. Due to the mobility and ruggedness of the handheld hardware, Raman spectroscopy can be used for police, firefighters, and military applications for identification of explosives and illicit drugs or warfare substances. With SERS (Surface Enhanced Raman Spectroscopy), Raman spectroscopy can even be used for trace analysis. The SERS effect enhances the sensitivity of the Raman signal by a factor of up to 107. This enables, for example, measuring pesticide residuals on fruit or vegetable surfaces for food safety. It can also be used to identify traces of drugs, e.g. in urine. However, one of the most common Raman-applications is the identity check or verification of incoming goods (RMID) in the pharma industries, directly in the warehouse. Users appreciate the ease of use and the ruggedness of the Raman hardware
Single-Use Technology Today – A Cornucopia of Applications
Full text linkWhether for classic biologics or advanced therapy medicinal products (ATMPs), laboratory applications, small-scale or large-scale productions, single-use technology (SUT), and its associated consumables are used everywhere. The advantages of deploying SUTs are well known. Wherever a single-use solution is available, it is tested and ultimately used. Based on milestones in the development of single-use systems and single-use platform technologies, this article provides an up-to-date overview of products available on the market and their manufacturers/suppliers. It also discusses process examples with SUTs, design options and configurations of single-use facilities and Switzerland’s pioneering role in the development and implementation of SUTs. In addition, the authors show that SUT has already been established beyond the biopharmaceutical sector
Control of Therapeutic Activity through Programmed Assembly
Full text linkThis review explores the control of therapeutic activity through programmed assembly of supramolecular systems. We examine the use of nucleic acids as scaffolds to create tailored assemblies of ligands, including glycan and peptide-based systems, drug-like small molecules or reagents for proximity-induced reactions. We discuss the principles of cooperativity in multivalent interactions, emphasizing their potential to enhance binding affinity and therapeutic efficacy and the opportunity to control their activity through strand displacement. We highlight seminal studies and illustrative case examples and address the challenges faced in translating these designs into clinical applications. Furthermore, we explore recent advancements that demonstrate successful in vivo applications, particularly in the context of anticoagulation therapies. This review aims to provide insights into the future of responsive therapeutic systems that leverage the programmability of supramolecular assemblies to develop potent and adaptable therapeutics
Oligonucleotide-based PROTACs to Degrade RNA- and DNA-Binding Proteins
Full text linkProteolysis targeting chimeras (PROTACs) are heterobifunctional molecules that sequester the endogenous protein degradation machinery of cells to induce degradation of targeted proteins. By bringing a target protein and a ubiquitin E3 ligase into close proximity, ubiquitin monomers can be transferred onto surface lysines of the protein, which is subsequently degraded by the proteasome. The functions of RNA- and DNA-binding proteins have been especially hard to modulate with small molecules. However, oligonucleotides that bind RNA- or DNA-binding proteins can be turned into oligonucleotide-based PROTACs to direct ubiquitination and degradation of these proteins. Here we summarize the current state of the field of oligonucleotide-based PROTACs that target RNA- or DNA-binding proteins
When DNA Repair Backfires – Trabectedin Induces DNA Breaks in Active Genes
Full text linkMany anticancer drugs are ineffective in tumors that have functional DNA repair mechanisms. In contrast, trabectedin, a tetrahydroisoquinoline alkaloid marine natural product, stands out as it is more lethal to cancer cells with active DNA repair, particularly transcription-coupled nucleotide excision repair (TC-NER), making it an intriguing alternative to standard chemotherapeutic agents. To optimize trabectedin’s use in precision oncology, it is essential to understand how its toxicity depends on TC-NER. In this study, we reveal that incomplete TC-NER of trabectedin-DNA adducts generates persistent single-strand breaks (SSBs). These adducts are found to obstruct the second of two sequential NER-mediated DNA incisions. By mapping the 3\u27-hydroxyl groups of SSBs resulting from the first NER incision at trabectedin-DNA adducts, we achieve genome-wide visualization of TC-NER. Our findings show that trabectedin-induced SSBs predominantly occur in the transcribed strands of active genes, accumulating near transcription start sites. This work provides new insights into how trabectedin can be leveraged for targeted cancer therapies and for studying TC-NER and transcription