Dan Klis

Imagine if you could turbocharge the speed of your flow cytometry analysis. 🤷 What if you could conduct your bench research the way you want to? Introducing the new Attune Xenith Flow Cytometer. The what if is here. Watch the full video: https://lnkd.in/gmms6wjU Experience the power of the Attune Xenith firsthand—request a demo today: https://lnkd.in/gZZeQPxt ​

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Happy Wednesday all! Check out this open access Cell Immunity review by Jason G. Cyster and Patrick C. Wilson, "Antibody modulation of B cell responses—Incorporating positive and negative feedback." Summary: Antibodies are powerful modulators of ongoing and future B cell responses. While the concept of antibody feedback has been appreciated for over a century, the topic has seen a surge in interest due to the evidence that the broadening of antibody responses to SARS-CoV-2 after a third mRNA vaccination is a consequence of antibody feedback. Moreover, the discovery that slow antigen delivery can lead to more robust humoral immunity has put a spotlight on the capacity for early antibodies to augment B cell responses. Here, we review the mechanisms whereby antibody feedback shapes B cell responses, integrating findings in humans and in mouse models. We consider the major influence of epitope masking and the diverse actions of complement and Fc receptors and provide a framework for conceptualizing the ways antigen-specific antibodies may influence B cell responses to any form of antigen, in conditions as diverse as infectious disease, autoimmunity, and cancer. #drugdiscovery #cancerresearch #antibodies #infectiousdisease #sarscov2 #autoimmunity #immunooncology #immunotherapy #scientificresearch

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Happy Tuesday all! Check out this open access Mol Therapy Nucleic Acids article by Delehedde et al., "Enhancing natural killer cells proliferation and cytotoxicity using imidazole-based lipid nanoparticles encapsulating interleukin-2 mRNA." Summary: mRNA applications have undergone unprecedented applications—from vaccination to cell therapy. Natural killer (NK) cells are recognized to have a significant potential in immunotherapy. NK-based cell therapy has drawn attention as allogenic graft with a minimal graft-versus-host risk leading to easier off-the-shelf production. NK cells can be engineered with either viral vectors or electroporation, involving high costs, risks, and toxicity, emphasizing the need for alternative way as mRNA technology. We successfully developed, screened, and optimized novel lipid-based platforms based on imidazole lipids. Formulations are produced by microfluidic mixing and exhibit a size of approximately 100 nm with a polydispersity index of less than 0.2. They are able to transfect NK-92 cells, KHYG-1 cells, and primary NK cells with high efficiency without cytotoxicity, while Lipofectamine Messenger Max and D-Lin-MC3 lipid nanoparticle-based formulations do not. Moreover, the translation of non-modified mRNA was higher and more stable in time compared with a modified one. Remarkably, the delivery of therapeutically relevant interleukin 2 mRNA resulted in extended viability together with preserved activation markers and cytotoxic ability of both NK cell lines and primary NK cells. Altogether, our platforms feature all prerequisites needed for the successful deployment of NK-based therapeutic strategies. #drugdiscovery #cancerresearch #immunotherapy #immunooncology #nkcells #gvhd #scientificresearch

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If you missed the latest Sustaining Barley webinar, head over to the AMBA website. Fertility, especially Nitrogen, is a huge component of the environmental impact of barley production. The presentations yesterday provided great insight on how to manage this impact. Thanks to Brady and Mike!

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In a recent Biocompare article, Application Scientist Supervisor Caroline Cardonnel explores the potentials and pitfalls of variable bandwidth in microplate readers: https://ow.ly/cUC650SJkmy. She highlights how, when used correctly, this feature can significantly enhance assay development by offering greater flexibility and sensitivity. However, improper use can lead to challenges that jeopardize signal integrity, data accuracy, and time efficiency. If you’re in the market for a microplate reader, read this first! #microplatereaders #variablebandwidth #IntheNews

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Happy Thursday all! Check out this open access Nature Leukemia review by Lei et al., "Leveraging CRISPR gene editing technology to optimize the efficacy, safety and accessibility of CAR T-cell therapy." https://lnkd.in/gAWFHq-j. Abstract: Chimeric Antigen Receptor (CAR)-T-cell therapy has revolutionized cancer immune therapy. However, challenges remain including increasing efficacy, reducing adverse events and increasing accessibility. Use of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology can effectively perform various functions such as precise integration, multi-gene editing, and genome-wide functional regulation. Additionally, CRISPR screening using large-scale guide RNA (gRNA) genetic perturbation provides an unbiased approach to understanding mechanisms underlying anti-cancer efficacy of CAR T-cells. Several emerging CRISPR tools with high specificity, controllability and efficiency are useful to modify CAR T-cells and identify new targets. In this review we summarize potential uses of the CRISPR system to improve results of CAR T-cells therapy including optimizing efficacy and safety and, developing universal CAR T-cells. We discuss challenges facing CRISPR gene editing and propose solutions highlighting future research directions in CAR T-cell therapy. #drugdiscovery #cancerresearch #crispr #tcelltherapy #immunooncology #immunotherapy #scientificresearch

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Happy Tuesday all! Hot off the presses is our new ADAR1 Activity TWO-Luciferase Reporter HEK293 Cell Line https://lnkd.in/gtu4gSNs Background: Adenosine Deaminase Acting on RNA (ADAR) enzymes perform adenosine to inosine base editing in RNA, especially targeting adenosines located within a specific double-stranded stem-loop motif (Figure 1). In healthy cells, ADAR1 activate a pro-inflammatory response through downstream dsRNA sensors. Loss-of-function mutations in ADAR1 result in aberrant activation of the dsRNA sensors and are involved in autoimmune disorders. ADAR1 dysfunction also impacts cancer cell growth, proliferation, and response to immunotherapy as ADAR1 expression is increased in many tumor types and ADAR1 KO has been shown to improve the response to immunotherapies such PD-1/PD-L1 blockade. The ability of ADAR1 activity to circumvent tumor resistance makes it an attractive target for therapeutic drug discovery, and this dual reporter cell line is an ideal tool to support that research. Please reach out to me for further information or a quote for this unique and innovative cell line to support your ADAR1 research!👩‍🔬 #drugdiscovery #cancerresearch #immunooncology #rnaediting #immunotherapy #icb #scientificresearch

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Happy Tuesday all! Check out this open access Cancer Cell paper by Seed et al., "Elucidating acquired PARP inhibitor resistance in advanced prostate cancer." https://lnkd.in/gJSkh8dJ Highlights: • Monitoring of PARPi-treated mCRPC detects the emergence of resistant subclones. • By 16 weeks, these associate with disease progression and survival. • BRCA2/PALB2 reversions in mCRPC present signs of microhomology-mediated repair. • Tumors with BRCA2 HomDels resist PARPi through the selection of BRCA2-competent cells. Looking for your PARPi small molecule breakthrough? Check out our unparalleled PARP & PARPTrap™ portfolio of biochemical and cellular assay kits and screening services to facilitate your early stage drug discovery pipeline: https://lnkd.in/g9kJrq6e #drugdiscovery #cancerresearch #parp #brca #immunooncology #scientificresearch

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Learn more about the Azenta Arc Automated Storage Family! 💊 ❄ 🔬 SampleArc systems are built for ambient to -20°C storage, BioArc systems for -80°C storage, and CryoArc systems for cryogenic temperature storage down to -190°C. Read more details below or let's connect on a call to discuss your storage needs!

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New research published in #NatureCommunicationsBiology maps the biophysical properties of natural and engineered antibodies, offering insights that could streamline antibody therapeutic development. This study enhances our understanding, improves design, and demonstrates the power of machine learning in antibody discovery. A must-read for those in the field! #AntibodyDiscovery #MachineLearning #Immunology #Antibody #Biophysics #Therapeutics #Biotechnology #Pharmaceuticals #DrugDevelopment 

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Hot off the presses! Are you utilizing minipigs in your AAV gene therapy research, or have you considered them as your larger animal model? Scientists at VRL Laboratories recently published in Viruses. Read more to learn why the Göttingen minipig might be a great choice for your next study. Prevalence of Antibodies against Adeno-Associated Viruses (AAVs) in Göttingen Minipigs and Its Implications for Gene Therapy and Xenotransplantation https://lnkd.in/g4KvFcFe

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Happy Friday all! Check out this open access Nature Scientific Reports article by Abali et al., "A nanowell platform to identify, sort and expand high antibody-producing cells." https://lnkd.in/gMuJNSxf Abstract: Increased use of therapeutic monoclonal antibodies and the relatively high manufacturing costs fuel the need for more efficient production methods. Here we introduce a novel, fast, robust, and safe isolation platform for screening and isolating antibody-producing cell lines using a nanowell chip and an innovative single-cell isolation method. An anti-Her2 antibody producing CHO cell pool was used as a model. The platform; (1) Assures the single-cell origin of the production clone, (2) Detects the antibody production of individual cells and (3) Isolates and expands the individual cells based on their antibody production. Using the nanowell platform we demonstrated an 1.8–4.5 increase in anti-Her2 production by CHO cells that were screened and isolated with the nanowell platform compared to CHO cells that were not screened. This increase was also shown in Fed-Batch cultures where selected high production clones showed titers of 19–100 mg/L on harvest day, while the low producer cells did not show any detectable anti-Her2 IgG production. The screening of thousands of single cells is performed under sterile conditions and the individual cells were cultured in buffers and reagents without animal components. The time required from seeding a single cell and measuring the antibody production to fully expanded clones with increased Her-2 production was 4–6 weeks. #drugdiscovery #antibodies #cancerresearch #immunotherapy #immunooncology #scientificresearch

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The Simoa® BD-Tau Advantage PLUS assay is paving the way for breakthroughs in Alzheimer's and other neurological conditions. 🧠 Discover how this assay is supporting research. #Biomarkers #Healthcare #BDTau #Alzheimers

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The Simoa® BD-Tau Advantage PLUS assay is paving the way for breakthroughs in Alzheimer's and other neurological conditions. 🧠 Discover how this assay is supporting research. #Biomarkers #Healthcare #BDTau #Alzheimers

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The Simoa® BD-Tau Advantage PLUS assay is paving the way for breakthroughs in Alzheimer's and other neurological conditions. 🧠 Discover how this assay is supporting research. #Biomarkers #Healthcare #BDTau #Alzheimers

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Happy Friday all! Check out this open access Nature article by Ferretti et al., "Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers." Abstract: The Werner syndrome RecQ helicase WRN was identified as a synthetic lethal target in cancer cells with microsatellite instability (MSI) by several genetic screens. Despite advances in treatment with immune checkpoint inhibitors, there is an unmet need in the treatment of MSI cancers. Here we report the structural, biochemical, cellular and pharmacological characterization of the clinical-stage WRN helicase inhibitor HRO761, which was identified through an innovative hit-finding and lead-optimization strategy. HRO761 is a potent, selective, allosteric WRN inhibitor that binds at the interface of the D1 and D2 helicase domains, locking WRN in an inactive conformation. Pharmacological inhibition by HRO761 recapitulated the phenotype observed by WRN genetic suppression, leading to DNA damage and inhibition of tumour cell growth selectively in MSI cells in a p53-independent manner. Moreover, HRO761 led to WRN degradation in MSI cells but not in microsatellite-stable cells. Oral treatment with HRO761 resulted in dose-dependent in vivo DNA damage induction and tumour growth inhibition in MSI cell- and patient-derived xenograft models. These findings represent preclinical pharmacological validation of WRN as a therapeutic target in MSI cancers. A clinical trial with HRO761 (NCT05838768) is ongoing to assess the safety, tolerability and preliminary anti-tumour activity in patients with MSI colorectal cancer and other MSI solid tumours. #drugdiscovery #cancerresearch #immunotherapy #immunooncology #syntheticlethal #scientificresearch

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