Jnana Therapeutics’ Post

📚 PUBLICATION ALERT | Blood-brain Barrier #organoids generated in #Gri3D plates with 600µm hydrogel microwells and imaging-bottom 💡Employing receptor-mediated transcytosis (RMT) emerges as an effective approach for delivering biologic agents across the blood-brain barrier (#BBB). The recent progression in creating human BBB organoid models is a significant breakthrough, aiding in understanding RMT mechanisms and expediting the development of brain delivery technologies for drug development. However, the existing techniques for generating organoids suffer from multiple limitations, preventing the use of #BBB organoids as a screening tool. 🚀 #Gri3D hydrogel-based arrays offer a 55-fold increase in organoid yield, addressing challenges of throughput and heterogeneity of #organoids. Paired with a custom semi-automated #imaging assay, our #scalable platform fast-tracks brain delivery tech development for early-stage drug discovery. 📄 Read the full publication from Roche scientists here: https://lnkd.in/eDg3sVsz 📩 Reach out if you want to learn more about the generation of #BBB organoids on Gri3D® plates! #DrugDelivery #BBBOrganoids #3DCellculture #InVitroModels #HighThroughput

I am excited to announce the publication of my latest paper titled "A Lipid-Based Delivery Platform for Thermo-Responsive Delivery of Teriparatide". https://lnkd.in/e4U3XExa   This work was a key part of my PhD research and a project I’ve been deeply passionate about. Herein we develop thermo-responsive teriparatide loaded liposomes as a potential pulsatile delivery system.   Key points of our research include: 📌 Hydrophobic ion pairing of teriparatide enhances peptide entrapment within liposomes 📌 Providing a first proof-of concept demonstrating the suitability of thermo-responsive liposomes as pulsatile delivery system 📌 Development of a cell-based receptor-binding assay to demonstrate retention of teriparatides biological activity   I'm very grateful to my co-authors for their support and contributions throughout this project: Wojciech Rozek, Ryan Mellor, Szymon W. Manka, Chris Morris, Steve Brocchini, and Gareth Williams.   #peptides #teriparatide #themoresponsive #liposomes #pulsatile #controlledrelease #DrugDelivery #PhD #cdt #research

Check out our two latest publications in American Chemical Society's Journal of Medicinal Chemistry and also Elsevier Antiviral Research (https://lnkd.in/eQNu73Uq) in collaboration with Arbutus Pharma for the development of selective and potent inhibitors of SARS-CoV-2 Mpro with pan-coronavirus activity. PROTEROS supported the discovery of these molecules by producing and purifying protein and associated off-target protein constructs for proteolytic inhibition and binding assays as well as ultra-pure protein for x-ray co-crystallography structures at 1.5-1.9 Å resolution (PDB code: 9GIL, 9GIJ 9GLV). AB-343 in particular demonstrated antiviral potency, selectivity, pan-coronavirus activity, and without requirement to boost with ritonavir, all of which differentiates from nirmatrelvir and ensitrelvir. This work with Arbutus Biopharma Corporation performed alongside X-Chem, Inc. is a testament to our commitment to collaborative partnerships that advance drug discovery. We consistently support biotech’s and pharma across the globe to enable the development of new therapeutics to patients. PROTEROS would like to thank our collaborators: Arbutus Biopharma Corporation, X-Chem and our team who worked on this project: Klaus Maskos, Franziska Preuss, Andreas Schmitt, Archna Prasad, Chia-yi Chen, Konstanze von König, Michael Blaesse, Andreas Bergman, Debora Konz Makino. Biological characterization of AB-343, a novel and potent SARS-CoV-2 Mpro inhibitor with pan-coronavirus activity https://lnkd.in/eg_tsJSk Biological Characterization of AB-343, a Novel and Potent SARS-CoV-2 Mpro Inhibitor with Pan-Coronavirus Activity - ScienceDirect of SARS-CoV-2 Mpro from a DNA-Encoded Chemical Library Screening Hit That Demonstrate Potent Inhibition against Pan-Coronavirus Homologues and Nirmatrelvir-Resistant Variants | Journal of Medicinal Chemistry https://lnkd.in/epfFvpBa #DrugDiscovery #COVID19 #Biophysics #ReachRightFaster #PROTEROS #StructuralBiology #assays #SARSCov2 #Mpro #HTS #XChem

Source: Xenobiotica; the fate of foreign compounds in biological systems Modeling compares ADC deconjugation and elimination rates using native LC-MS data from human plasma. It analyzes inter-chain cysteine conjugated ADCs, focusing on drug linker deconjugation, hydrolysis, and clearance. Findings show similar in vitro rates for MMAE and MMAF ADCs, but pronounced in vivo clearance for MMAE. This study presents novel affinity capture LC-MS analysis and modeling of drug load species using clinical data.

Want to learn how capillary LC-MS is shaping the future of #DrugDevelopment? Join our Oct. 17th webinar hosted by Separation Science to explore our Lipidomics Analytical Platform for #mRNA #LNP Innovation and its role in regulatory approval and learn LC-MS techniques for studying organoids and organ-on-chip models. Key Takeaways: • Sensitive LC-MS analysis • Customized sample prep • Method validation tips #LCMS

#Article Field-Portable Leukocyte Classification Device Based on Lens-Free Shadow Imaging Technique by Hyun-Sik Jung and Sungkyu Seo https://lnkd.in/gpGfqUHK   #MDPI #Imaging #Biochemical #CMOS #biosensors #sensors #openaccess   #Abstract The complete blood count (CBC) is one of the most important clinical steps in clinical diagnosis. The instruments used for CBC are usually expensive and bulky and require well-trained operators. Therefore, it is difficult for medical institutions below the tertiary level to provide these instruments, especially in underprivileged countries. Several reported on-chip blood cell tests are still in their infancy and do not deviate from conventional microscopic or impedance measurement methods. In this study, we (i) combined magnetically activated cell sorting and the differential density method to develop a method to selectively isolate three types of leukocytes from blood and obtain samples with high purity and concentration for portable leukocyte classification using the lens-free shadow imaging technique (LSIT), and (ii) established several shadow parameters to identify the type of leukocytes in a complete leukocyte shadow image by shadow image analysis. The purity of the separated leukocytes was confirmed by flow cytometry. Several shadow parameters such as the “order ratio” and “minimum ratio” were developed to classify the three types of leukocytes. A shadow image library corresponding to each type of leukocyte was created from the tested samples. Compared with clinical reference data, a correlation index of 0.98 was obtained with an average error of 6% and a confidence level of 95%. This technique offers great potential for biological, pharmaceutical, environmental, and clinical applications, especially where point-of-care detection of rare cells is required.

Greetings Connections! Interesting to share my molecular docking experiences with you all! I am performing rigid docking for different oncoproteins with some of the FDA-approved chemotherapeutic drugs as my receptor and ligand. Here, I have performed molecular docking of the PALB2/BRCA2 complex with Abemaciclib drug and analyzed it on Discovery Studio and we can visualize the receptor-ligand interactions on a 2D diagram. I am overwhelmed to share my learnings with you all! Thanks & Regards. #bioinformatics #moleculardocking #oncoproteins #cancergenetics #computationalbiology

📢 Publication alert As 2024 came to an end, the latest article of my PhD was recently published in Bio&Bio. In this work, we establish a novel mechanistic model for the antibody disulfide bond reduction reaction, a critical step for cysteine-based antibody-drug conjugates (ADCs). 🔬 Key highlights: - Developed a reduction kinetic model describing effects of reduction agent excess and temperature on the disulfide bond reaction kinetics - Introduced a cross-analytical approach combing capillary gel electrophoresis (CGE) and reversed-phase chromatography to accurately predict the drug-to-antibody-ratio (DAR) and drug load distribution (DLD) - Built an integrated modeling framework that connects reduction and conjugation steps, enabling the prediction of DAR/DLD directly from initial reduction conditions - Demonstrated the potential for in-silico screening to optimized reduction parameters. Our findings pave the way for more mechanistic-driven process optimization for ADCs while reducing experimental effort. A huge thanks to my co-authors Pedro González, Kimberly Hui, Michaela Wendeler and Jürgen Hubbuch. If you are interested in learning more, feel free to check out the full paper here: https://lnkd.in/ezaNu4vG

Want to learn how capillary LC-MS is shaping the future of #DrugDevelopment? Join our Oct. 17th webinar hosted by Separation Science to explore our Lipidomics Analytical Platform for mRNA LNP Innovation and its role in regulatory approval and learn LC-MS techniques for studying organoids and organ-on-chip models. Key Takeaways: • Sensitive LC-MS analysis • Customized sample prep • Method validation tips

Want to learn how capillary LC-MS is shaping the future of #DrugDevelopment? Join our Oct. 17th webinar hosted by Separation Science to explore our Lipidomics Analytical Platform for mRNA LNP Innovation and its role in regulatory approval and learn LC-MS techniques for studying organoids and organ-on-chip models. Key Takeaways: • Sensitive LC-MS analysis • Customized sample prep • Method validation tips