Matthias Haury

Heterogeneity of solid tumors, composed of different cells spatially organized… Tumor ecosystems vs. cell autonomy… Including extracellular matrix…

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🔍 𝐄𝐱𝐩𝐥𝐨𝐫𝐢𝐧𝐠 𝐭𝐡𝐞 𝐅𝐫𝐨𝐧𝐭𝐢𝐞𝐫𝐬 𝐨𝐟 𝐑𝐍𝐀 𝐃𝐞𝐥𝐢𝐯𝐞𝐫𝐲 𝐰𝐢𝐭𝐡 𝐋𝐢𝐩𝐢𝐝 𝐍𝐚𝐧𝐨𝐩𝐚𝐫𝐭𝐢𝐜𝐥𝐞𝐬 🧬 Exciting developments in nanomedicine continue to shape our approach to disease treatment, particularly through the use of lipid nanoparticles (LNPs) in RNA delivery. It's crucial to understand the foundational aspects that make LNPs an effective tool in gene therapy and beyond. This insightful review dives deep into the mechanics and applications of LNPs, highlighting the meticulous process of lipid component selection and encapsulation strategies that form the foundation of LNP development. It further elaborates on the importance of characterizing and optimizing these particles to ensure effective delivery, while also detailing the transition from in vitro studies to human clinical trials. 🎯 𝐊𝐞𝐲 𝐓𝐚𝐤𝐞-𝐚𝐰𝐚𝐲𝐬: • 𝐵𝑖𝑜𝑐𝑜𝑚𝑝𝑎𝑡𝑖𝑏𝑖𝑙𝑖𝑡𝑦 𝑎𝑛𝑑 𝑉𝑒𝑟𝑠𝑎𝑡𝑖𝑙𝑖𝑡𝑦: LNPs provide a safe and adaptable platform for RNA delivery, crucial for treatments across various diseases. • 𝐶𝑟𝑢𝑐𝑖𝑎𝑙 𝑆𝑡𝑎𝑔𝑒𝑠 𝑜𝑓 𝐷𝑒𝑣𝑒𝑙𝑜𝑝𝑚𝑒𝑛𝑡: From the formulation of LNPs to their characterization and in vivo evaluation. • 𝑃𝑟𝑜𝑚𝑖𝑠𝑖𝑛𝑔 𝐴𝑝𝑝𝑙𝑖𝑐𝑎𝑡𝑖𝑜𝑛𝑠: Beyond their success in COVID-19 vaccines, LNPs are being explored for a wide range of therapies, including cancer immunotherapies and genetic disorders. • 𝐹𝑢𝑡𝑢𝑟𝑒 𝑂𝑢𝑡𝑙𝑜𝑜𝑘: The field is set to expand with ongoing research into enhanced delivery mechanisms and broader therapeutic applications. For those at the cutting edge of RNA-based therapies, this review is an essential resource. 🔗 Here's the link to the full publication (open access): https://lnkd.in/gDVx4gdX #Nanomedicine #RNATherapeutics #LipidNanoparticles #GeneTherapy #Biotechnology #DrugDelivery #mRNA #InnovativeMedicine #HealthcareInnovation #ScientificResearch Yutian Ma, Shiyao Li, Xin Lin & Yupeng Chen

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NPC's - #LLM and Chronicling a realm where input signals aren't confined to customary data sources but diffused across disparate computational dimensions, super prompts are conferred dominion over a maelstrom of #information – encompassing both structured datasets and amorphous text corpora. This multidimensional panorama bestows upon them the capacity to harmonize an eclectic assortment of #data, affording outputs that are both recondite in their #wisdom and highly pertinent to their respective contexts.

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RNA Horizons 2024 in Porto! https://rnahorizons.com/ I am super excited to present RNAble's recent data to RNA-therapeutics leaders. Building upon the groundbreaking developments of 2020, the symposium will convene a diverse array of experts, including RNA biologists, systems analysts, immunologists, and drug development specialists. Fostering a collaborative environment, this event will facilitate the exchange of cutting-edge research, the development of a unified scientific lexicon, and the acceleration of research and development efforts in RNA therapeutics. Key thematic areas of exploration will encompass: RNA system biology, including methods to sequence and identify RNA splicing, editing, and processing in health and disease. Expanding the scope of RNA therapeutics: RNA splicing and processing in health and disease. https://lnkd.in/d5p_FUfX

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We are excited to be able to provide sustainable solutions to the Brazilian growers. Brazil's biologicals market is growing rapidly, with a 15% increase in the 2023/2024 harvest, generating BRL 5 billion (USD 892 million) in sales. Biocontrol products like biofungicides, insecticides, and nematicides dominate 80% of the market. By 2030, the market is expected to reach BRL 17 billion (USD 3 billion). Ginkgo Bioworks has entered Brazil through partnerships, providing R&D services using a variety of capabilities and developing a broad range of product concepts, fitting various regulatory frameworks. We work with microorganisms to develop agricultural solutions, including biofungicides. For example, we collaborate with Agrivalle focusing on enhancing existing products, while we partner with the Centro de Tecnologia Canavieira to modify sugarcane to resist pests like the sugarcane weevil using genetic engineering techniques. https://lnkd.in/gicij_ks

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Paper Review of IgY Antibodies as Biotherapeutics in Biomedicine The paper authored by @Diana León-Núñez, María Fernanda Vizcaíno-López, and their team offers an insightful perspective on the potential of IgY antibodies derived from birds. It underscores their significant role in crucial human medicine experimentation, diagnosis, and treatment while emphasizing their unique characteristics. The realm of IgY technology is not just promising but is also witnessing rapid expansion. The global interest in this field is palpable, with over a thousand scientific articles related to IgY technology published to date. The publication surge since 2008 is noteworthy, with researchers from China, the United States, Canada, Japan, and Germany at the forefront. IgYs exhibit crucial structural and functional differences compared to IgGs. While both are composed of two light chains and two heavy chains, IgYs lack the hinge region, limiting their flexibility. This characteristic renders them highly specific and more resistant to proteolytic degradation. IgYs are safer than IgGs as they do not bind to human Fc receptors or fix mammalian complement components; hence, they do not induce dangerous immune responses. The structural attributes and production process of IgYs present several advantages over mammalian IgGs, including: A robust immune response against epitopes of conserved mammalian proteins, typically not immunogenic in other mammalian species due to their high homology. Reduced cross-reactivity. Avoidance of human complement activation. A decrease in false positives owing to the absence of rheumatoid factor binding sites in the Fc region. No toxic side effects were reported for therapeutic uses. Low-cost extraction and a higher yield of IgY antibodies from egg yolks (15 mg/egg). The authors propose using IgY as an antitumor agent due to its ability to induce apoptosis in cancer cells when directed against TRAIL-2R. They also suggest its application as a novel immunotherapeutic molecule against cancer stem cells in treating glioblastoma, using IgY anti-CD133, a marker characteristic of these cells. However, like mouse IgGs, they may be subject to elimination by immunogenicity processes. IgYs also can target a wide range of antibiotic-resistant bacteria.  In conclusion, IgY antibodies, whether polyclonal or monoclonal, can target conserved mammalian proteins with rare cross-reactions in diagnosis, as they are not the targets of the rheumatoid factor. Furthermore, they do not induce complement activation, making them suitable for treatment and prophylaxis. The use of IgYs as reagents for PK and ADA PCs is well-established, and their usage has increased significantly over the past five years. With all the new biological therapeutics, I would read this paper! #IgY, #Biotherapeutics, #Antibodies, #Pharmacokinetics, #ADA, #Immunogenicity, #Pharmacodynamics, #Biotech You can download the paper here: https://lnkd.in/eHVKJe3g

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The manufacturing process of CAR T cells plays a critical role in the clinical impact by influencing the phenotype and function. The process involves isolation of the starting population, T-cell activation, genetic modification, ex vivo expansion, formulation, and product release. In this article, the authors focused on autologous CAR-T cell manufacturing.   The first step involves isolating the starting cell population. After apheresis is collected cell isolation is achieved commonly through MACs separation through negative or positive selection. Currently approved CAR T cell products contain both CD4+ and CD8+ cells, among CD19 CAR T cell products Tisa-cell, Axi-cel, and Brexu-cel utilized mixed CD4+ and CD8+ T cells, in contrast, Liso-cel comprises two different products made separately from CD4+ and CD8+ populations that are admixed prior administration. Regarding T cell phenotypes, T naïve cells and T memory subsets possess a greater potential for long-term persistence and produce lower levels of inflammatory cytokines avoiding toxicities such as cytokine release syndrome   The second step involves T-cell activation. T-cell activation is mostly achieved through anti-CD3/anti-CD28 coated magnetic beads or nanomatrices. Magnetic beads are prone to engulfment by myeloid cells, thus posing a risk of contamination of CD14+ in the purified population and reducing the reagent available for activation. Nanomatrices appear less prone to elimination by myeloid cells and can be removed by simple centrifugation. Although T cell activation is a critical step in CAR T cell manufacturing next-generation manufacturing processes are contemplating the possibility of eliminating T cell activation   The third process is the introduction of CAR transgene either by viral or non-viral delivery. Viral delivery is beneficial because of high integration efficiency and persistence, however, viral transduction lacks insertion-site specificity presenting a risk for insertional mutagenesis.  Non-viral delivery can be achieved by CRISPR/CAS9 or transposon system. CRISPR/CAS9 can specify the transgene integration, on the opposite side, transposon systems transgene integration is not specific raising concerns about insertional mutagenesis.   The fourth process is the ex-vivo expansion.  Typically, the expansion period varies between 1-2 weeks, the expansion protocol allows the elimination of non-T cells by exposing them to inadequate culture conditions. However, next-generation protocols can generate products within as few as 24h, but this short time limits the cell count that can be accomplished   The last step is product release, all products must comply with defined product characteristics such as safety, purity, potency, identity, and stability #CARTcells #Cancerresearch #Celltherapy  

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Unraveling the Mysteries of Molecular Dynamics: #MDverse Sheds Light on Dark Matter! MDverse indexes and curates over 250,000 molecular dynamics files from open repositories like Zenodo, Figshare, and OSFramework. Using MDverse Data Explorer, researchers can explore this data collection quickly. Quick Read: https://lnkd.in/gaF-RVrp #bioinformatics #moleculardynamics #structuralbiology #sciencenews

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🧬 New Tool in Spatial Transcriptomics: Explore Cell Niches with NicheCompass 🌐 The bioRxiv publication "Quantitative characterization of cell niches in spatial atlases." by Sebastian Birk and colleagues introduces NicheCompass, a bio-inspired graph learning method to understand cellular microenvironments. 🔍 What is NicheCompass? 📈 Utilizes graph deep learning to map and characterize cell niches, leveraging cellular communication and spatial gene programs. 🚀 Tested on a whole mouse brain atlas, integrating data from 8.4 million cells across various spatial transcriptomics platforms. 🪄 Multimodal Integration: Enhances niche characterization by combining gene expression with chromatin accessibility data. 🔬 Introudces fine-tuning-based spatial reference mapping to uncover and detail novel cell niches in complex tissues. 📚 bioRxiv paper: https://buff.ly/3Uno16x 👨‍💻 GitHub: https://buff.ly/4ccBsgF 📢 Join the Conversation 📢 What tools are you using in your spatial analyses? Share your ideas, methods, and tools in the comments! 👇 💬 #SpatialTranscriptomics #CellBiology #Bioinformatics #Genomics #NicheCompass #DataScience

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We are excited to share our latest research about hepatitis D genetic variability in Brazil. This is the first study to provide extensive information about complete genome sequences from our country. You don't want to miss it! Check out the paper here: https://lnkd.in/dTfMkc6H

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#Cancer | #OncoMimics | A "Mimicry-Based" Strategy between Human & Commensal Ags for the Development of a New Family of #ImmuneTherapies | Breaking Preprint from Joao G. Magalhaes & Co. at BioRxiv 👏 | #TAAs | Peptide vaccines have emerged as a promising strategy for cancer immunotherapy, yet often lack of strong, specific and sustained immune responses against tumor antigens. To achieve a robust immune response, the effective selection of tumour antigens is crucial. While neoantigens trigger potent immune responses, their use suffers from patient specificity and their rarity in low-mutational tumors. Alternatively, the immunogenic potential of tumor-associated antigens (TAAs) is limited by central immune tolerance. Molecular mimicry and T cell cross-reactivity is a proposed mechanism to trigger a robust T cell-mediated antitumor response. Although molecular mimicry between pathogens and tumor antigens has been described, the potential benefits of exploiting this molecular mimicry with commensal bacterial antigens in antitumor immunity have not been thoroughly investigated despite strong evidence that the composition of the human microbiota significantly influences immune competency. Here*, Alice Talpin - Le Borgne, et al describe a new approach called OncoMimics, which uses molecular mimicry between commensal bacterial and tumoral antigens to induce cross-reactive cytotoxic T cells against tumor cells. In preclinical studies, vaccination with OncoMimic peptides (OMPs) led to the expansion of CD8+ T cells reacting against homologous tumor-associated antigen peptides and elicits cytotoxic activity against tumor cells. OMPs are efficiently recognized by a prevalent T cell population within the peripheral blood mononuclear cells of healthy individuals. An ongoing clinical trial (NCT04116658) using OncoMimics in patients with glioblastoma demonstrates early, durable, and cross-reactive tumor antigen CD8+ T cell responses with pronounced memory persistence. By overcoming the current vaccine limitations, OncoMimics constitutes a promising strategy for enhancing cancer immunity and improving patient outcomes. *https://lnkd.in/enWFyqd4 Celentyx Ltd #immunooncology www.celentyx.com Professor Nicholas Barnes PhD, FBPhS Omar Qureshi Catherine Brady GRAPHICAL ABSTRACT | From Enterome website | https://lnkd.in/eVX5f8Fb |

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This was an important meeting (i am sorry i could not go this time) for the advancement of #genomics in #LatinAmerica. In the link provided by Anna Laura Ross you can see the agenda and you can also see all the videos from the presentations The meeting was organized by the Pan American Health Organization and the objectives were: 1. To raise awareness about #genomics and about the World Health Organization Science Council report on #genomics and global health 2. To share experiences and best practices in the implementation of genomics for #precisionhealth and for #publichealth 3. To identify challenges and feasible strategies for the implementation of genomics 4. To create opportunities for linkages and collaborations Please share this important materials and information with your network. #genomics #genomicsforall #genomicmedicine #genomicresearch #genome #clinicalgenomics #globalhealth Elena Ambrosino Sasha Peiris MD, MPH Iscia Lopes-Cendes Gabriela Repetto Sherry Taylor PhD, FCCMG, ErCLG

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So excited to share our recent publication on the groundbreaking advancements in human #mesenchymal stromal cells (hMSCs) research for manufacturing of #extracellular vesicles (EVs). Over the past 20 years, hMSCs have been pivotal in cell therapy, primarily due to their paracrine signalling mechanisms. Our study breaks new ground by demonstrating that human #telomerase reverse transcriptase (hTERT) immortalised #hMSCs can be adapted to suspension culture, eliminating the need for #microcarriers or other matrices to support cell growth. Key Highlights 🏄‍♂️ 🌷 Novel Cell Line: Introducing suspension hMSCs (S-hMSCs) with a doubling time of approximately 55 hours. 🌷Immunophenotype: Retains nearly 90% of CD73 and CD105 expression levels, with notable upregulation of CD44, CD46, and CD47. 🌷EV Production: Generates extracellular vesicles (EVs) in a chemically defined medium, averaging 150 nm in size, displaying key markers like CD63, CD81, and TSG101. 🌷Process Development: S-hMSCs offer immense potential for drug discovery and translational studies in the EV field. Proud to be part of this innovative research that paves the way for future breakthroughs in biotechnology and cell / cell-free therapies! Congratulations to this wonderful team of extraordinary researchers and bioengineers whom I’ve had the pleasure of working alongside on this project and others from the UCL Department of Biochemical Engineering, Cell and Gene Therapy / Regenerative Medicines Group. Pedro Silva Couto, PhD Dale Stibbs, PhD Braulio Carrillo Sanchez, PhD Ben Barnes, PhD Rana Khalife, PhD Theano Panagopoulou, PhD #Biotech #CellTherapy #ResearchInnovation #HumanMSCs #EVs #DrugDiscovery #TranslationalResearch #ScientificBreakthroughs #LifeSciences #InnovationInScience

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50 𝐬𝐡𝐚𝐝𝐞𝐬 𝐨𝐟 𝐀𝐈 𝐢𝐧 𝐫𝐞𝐠𝐮𝐥𝐚𝐭𝐨𝐫𝐲 𝐬𝐜𝐢𝐞𝐧𝐜𝐞 As we know, there are numerous categories and definitions of #AI. In collaboration with Tong Weida, we authored an editorial on this topic to spark a discussion within the field of regulatory science. This article will be open access until August 11 here: https://lnkd.in/eAM8xzH2 I invite you to share your thoughts on the definitions and applications we presented. Here are some of the highlights from the article to entice you check it out in case title was not sufficient :) • AI integration in regulatory science advances how regulatory bodies approach review, oversight, compliance, and innovation. • AI's roles in regulatory applications include assisting, augmenting, autocratic, and autonomous, each with distinct implications. • Understanding AI's context-of-use is crucial to address biases, ensure transparency, and enhance decision-making in regulatory frameworks. • We stress tailored regulations for AI's diverse roles to ensure it enhances, not complicates, regulatory processes. • Governance frameworks must adapt to varying human-AI interaction levels, promoting responsible and ethical AI integration in #regulatoryscience .

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Bridge Editing: The Future of Gene Editing After Crispr Cas Chapter 1: The Power of Rewriting Life's Code, The evolution of CRISPr and the Innovation of Bridge Editing Chapter 2: A Revolutionary Tool with Limitations Chapter 3: A New Era of Precision Chapter 4: How Bridge Editing Works Chapter 5: The Molecular Architecture of Bridge Editing Chapter 6: The Vision of Biotechnology Reviews For the full length article Bridge Editing: The Future of Gene Editing After Crispr Cas, check out https://lnkd.in/d4vgFeYD

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Bridge Editing: The Future of Gene Editing After Crispr Cas Chapter 1: The Power of Rewriting Life's Code, The evolution of CRISPr and the Innovation of Bridge Editing Chapter 2: A Revolutionary Tool with Limitations Chapter 3: A New Era of Precision Chapter 4: How Bridge Editing Works Chapter 5: The Molecular Architecture of Bridge Editing Chapter 6: The Vision of Biotechnology Reviews For the full length article Bridge Editing: The Future of Gene Editing After Crispr Cas, check out https://lnkd.in/d4vgFeYD

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RE-EMERGENCE OF OROPUCHE VIRUS- BRAZIL 2024 - EPI STUDY!!! NICE READING!!!! Overall, 8639 (81·8%) of 10 557 laboratory-confirmed Oropouche fever cases from Jan 4, 2015, to Aug 10, 2024, occurred in 2024, which is 58·8 times the annual median of 147 cases (IQR 73–325). Oropouche virus infections were reported in all 27 federal units, with 8182 (77·5%) of 10557 infections occurring in North Brazil. We detected Oropouche virus RNA in ten (11%) of 93 patients with acute febrile illness between Jan 1 and Feb 4, 2024, in Amazonas state. AM0088 had a significantly higher replication at 12 h and 24 h after infection in mammalian cells than the prototype strain. AM0088 had a more virulent phenotype than the prototype in mammalian cells, characterised by earlier plaque formation, between 27% and 65% increase in plaque number, and plaques between 2·4-times and 2·6-times larger. Furthermore, serum collected on May 2 and May 20, 2016, from individuals previously infected with Oropouche virus showed at least a 32-fold reduction in neutralizing capacity (i.e., median PRNT50 titre of 640 [IQR 320–640] for BeAn19991 vs <20 [ie, below the limit of detection] for AM0088) against the reassortant strain compared with the prototype.

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