Hongene Biotech Corporation

We are thrilled to introduce 𝗛𝗶𝗫𝗖𝗮𝗽™——Novel cap analog designs developed by Hongene for enhanced mRNA immune evasion🎉! Rapid advancements in the mRNA therapeutics field underscore the potential of this groundbreaking technology to address medical needs across multiple disease areas and the critical role of ongoing innovation. At the cutting edge of mRNA innovation, we strive to enhance the efficacy, safety, and overall impact of mRNA-based treatments. Our goal is to deliver unparalleled value to patients and our collaborators, pushing the boundaries of what's possible in therapeutic development. The chemistry of the 5' mRNA end cap is crucial for stability and translation of mRNA drug modalities. Designed to enhance translation efficiency during immune stress, our HiXCap™ novel cap structures offer a promising solution for improving mRNA-based therapeutics. Studies carried out in 𝑖𝑛 𝑣𝑖𝑡𝑟𝑜 and 𝑖𝑛 𝑣𝑖𝑣𝑜 inflammation models have demonstrated their potential to transform treatment outcomes. As we look to the future, we are confident that studies in NHPs and human clinical trials will reveal even more pronounced advantages of HiXCap™ structures, ultimately enhancing treatment outcomes across a wide range of disease indications! Download our latest brochure to explore more about our innovative solution👇. Connect with our experts today 👉https://lnkd.in/ejdFEmsE. #mRNA #RNAtherapeutics #mRNAcapping #mRNACDMO

A recent study has identified and characterized a long-sought enzyme, Pyrimidine Nucleoside 2′-Hydroxylase (PDN2′H), which has significant implications for the development of therapeutic nucleoside analogs. The functionalization of nucleosides at the 2′-position is crucial for tailoring their pharmacological properties. Despite the importance of this modification, the chemical synthesis of 2′-functionalized nucleosides remains challenging. Enzymatic approaches, particularly those involving the nucleoside salvage pathway (NSP), offer a promising alternative. Over 50 years ago, PDN2′H activity was described in fungal species, but the corresponding protein sequences and detailed characterization were never reported. Led by researchers from The University of Freiburg, this study aims to fill this gap by identifying and characterizing PDN2′H from Neurospora crassa. The researchers identified the gene encoding PDN2′H in the genome of Neurospora crassa through computational analysis and confirmed its 2′-hydroxylation activity using NMR spectroscopy. They also explored the substrate scope of PDN2′H, revealing its preference for various pyrimidine nucleosides. The study successfully identified and characterized PDN2′H from Neurospora crassa, confirming its role in hydroxylating thymidine at the α-2′-position. The enzyme exhibited regio- and stereoselectivity for the α-2′-position, supporting its role in the nucleoside salvage pathway. The substrate scope analysis showed that PDN2′H accepted various derivatives of thymidine but was selective against compounds with substantial deviations from the natural substrate. The crystal structure revealed that the nucleobase is the primary substrate recognition factor, and the 3′-endo sugar conformation accounts for the regioselectivity. This study not only solves a long-standing mystery in enzymology but also provides a valuable tool for the biocatalytic synthesis of therapeutic nucleoside analogs, potentially leading to new treatments for cancer and viral infections. Congratulations to all contributors🎉! Ferdinand Genz Oliver Einsle Manfred Jung Nico Fessner Find out more: https://lnkd.in/gwxdNpVf #therapeuticnucleosides #nucleoside #nucleicacids #biocatalysis #RNAtherapeutics

Designed to enhance translation efficiency during immune stress, our 𝗛𝗶𝗫𝗖𝗮𝗽™ novel cap structures offer a promising solution for improving mRNA-based therapeutics! ✅ 𝗘𝗻𝗵𝗮𝗻𝗰𝗲𝗱 𝗧𝗿𝗮𝗻𝘀𝗹𝗮𝘁𝗶𝗼𝗻 𝗘𝗳𝗳𝗶𝗰𝗶𝗲𝗻𝗰𝘆 ✅ 𝗥𝗼𝗯𝘂𝘀𝘁 𝗣𝗲𝗿𝗳𝗼𝗿𝗺𝗮𝗻𝗰𝗲 𝗔𝗰𝗿𝗼𝘀𝘀 𝗘𝘅𝗽𝗲𝗿𝗶𝗺𝗲𝗻𝘁𝘀 ✅ 𝗩𝗲𝗿𝘀𝗮𝘁𝗶𝗹𝗶𝘁𝘆 𝗶𝗻 𝗺𝗥𝗡𝗔 𝗗𝗿𝘂𝗴 𝗠𝗼𝗱𝗮𝗹𝗶𝘁𝗶𝗲𝘀 These cap analogs demonstrated excellent performance in IVT reactions and improved translation efficiency in immune-stimulated cells and in 𝑖𝑛 𝑣𝑖𝑣𝑜 inflammation models. Their versatility and compatibility with various mRNA drug modalities make them a valuable tool for the development of mRNA-based therapeutics！ Download our latest brochure to explore our innovative solution more: https://lnkd.in/egAscUFG! #mRNA #RNAtherapeutics #mRNAcapping #mRNACDMO

A new study presents a novel method for noninvasive visualization of mRNA vaccine antigen expression in vivo, leveraging PET/CT imaging technology. The study demonstrates the potential of using a genetically fused PET reporter gene to monitor the spatiotemporal dynamics of mRNA vaccine antigen expression, which could significantly impact the development and evaluation of future mRNA vaccines. Current methods for assessing mRNA vaccine expression are invasive and do not allow for longitudinal monitoring. Noninvasive imaging techniques, such as PET/CT, offer a solution by providing quantitative measures of radiotracer accumulation in tissues. Led by researchers from the University of Pennsylvania, this study explores the use of a PET reporter gene, eDHFR (Escherichia coli dihydrofolate reductase), to monitor mRNA vaccine antigen expression in vivo. The researchers genetically fused eDHFR to the delta furin diproline modified SARS-CoV-2 spike glycoprotein (S2PΔf) mRNA vaccine and imaged its expression in female mice and male non-human primates using [18F]fluoropropyl-trimethoprim ([18F]FP-TMP). The study involved intramuscular administration of mRNA-LNPs (lipid nanoparticles) and PET/CT imaging at various time points to assess the distribution and persistence of the vaccine antigen. The immunogenicity of the S2PΔf-eDHFR fusion protein was also evaluated through ELISA and T cell polyfunctionality assays. 🔍 Key Findings: ✅ Transient expression of the vaccine antigen was observed in the injection site and draining lymph nodes. ✅ The eDHFR fusion did not impact the immunogenicity of the spike protein. ✅ No immune response was detected against eDHFR, ensuring the safety and efficacy of the approach. ✅PET/CT imaging provided high-resolution, quantitative data on antigen expression over time. This innovative imaging technique could revolutionize the way we develop and evaluate mRNA vaccines. By allowing noninvasive, longitudinal monitoring of antigen expression, researchers can gain deeper insights into mRNA pharmacokinetics and pharmacodynamics, ultimately leading to more effective and targeted therapies. Congratulations to all contributors🎉! Mark Sellmyer Mohamad-Gabriel Alameh Gabrielle Blizard Garima D. Hooda Said, Yi-Kan Pan Find out more: https://lnkd.in/ge2HEFhe #mRNAVaccine #vaccinedevelopment #RNAtherapeutics #LNPs #proteinexpression

💡Unlocking the Future of Vaccines with Self-Amplifying RNA Technology——A recent review article highlights the significant progress and potential of self-amplifying RNA (saRNA) vaccines, a technology that could revolutionize how we combat infectious diseases. Vaccines are a cornerstone of global health, yet many pathogens still lack effective vaccines. The COVID-19 pandemic underscored the urgent need for rapid, scalable, and potent vaccine platforms. Enter self-amplifying RNA (saRNA) vaccines, which leverage intracellular RNA amplification to achieve robust antigen expression at lower doses, offering a promising solution. 📚 Key Insights from the Review: ✔ 𝗩𝗲𝗰𝘁𝗼𝗿 𝗗𝗲𝘀𝗶𝗴𝗻 𝗮𝗻𝗱 𝗢𝗽𝘁𝗶𝗺𝗶𝘇𝗮𝘁𝗶𝗼𝗻: The review delves into the design of saRNA vectors derived from alphaviruses like VEEV, SINV, and SFV. These vectors enable efficient antigen expression and immune response. ✔ 𝗠𝗲𝗰𝗵𝗮𝗻𝗶𝘀𝗺 𝗼𝗳 𝗔𝗰𝘁𝗶𝗼𝗻: saRNA vaccines trigger both innate and adaptive immune responses, enhancing their efficacy. The review explains how these vaccines can be formulated with various delivery systems, including lipid nanoparticles (LNPs) and polymeric nanoparticles. ✔ 𝗖𝗹𝗶𝗻𝗶𝗰𝗮𝗹 𝗣𝗿𝗼𝗴𝗿𝗲𝘀𝘀: The first saRNA vaccine, KostaiveⓇ, has been approved in Japan and the European Union, marking a significant milestone. Clinical trials have shown that saRNA vaccines can induce strong immune responses and protect against pathogens like SARS-CoV-2. ✔ 𝗖𝗵𝗮𝗹𝗹𝗲𝗻𝗴𝗲𝘀 𝗮𝗻𝗱 𝗦𝗼𝗹𝘂𝘁𝗶𝗼𝗻𝘀: While saRNA vaccines show great promise, challenges remain. These include optimizing delivery systems, ensuring stability, and addressing safety concerns related to innate immune responses. The review discusses strategies to mitigate these challenges, such as using modified nucleotides and optimizing vector design. The review underscores the transformative potential of saRNA vaccines to shape the future of immunization strategies, particularly in response to pandemics and other global health threats. It emphasizes the need for continued research and development to optimize saRNA technology, improve delivery systems, and mitigate challenges. The insights provided in this review are crucial for advancing the field of saRNA vaccines, which could revolutionize not only the fight against infectious diseases but also broader applications in immunotherapy, such as cancer treatment. Congratulations to all contributors Credo Casmil Hyunjoo Cha-Molstad Anna Blakney 🎉! Find out more: https://lnkd.in/eDfwEJ45 #saRNA #RNAtherapeutics #vaccinedevelopment #infectiousdisease #drugdevelopment

Greetings from Copenhagen 🌟! Today marks the final day at the 2nd CRISPR MEDiCiNE Conference. Our Vice President of EU Market Dr. Michael Leuck and mRNA Technical Sales Specialist Dr. Lisa Bornewasser have been having delightful conversations and are eager to connect with even more of you！ Visit us at our cozy corner, 𝗯𝗼𝗼𝘁𝗵 #𝗖-𝟯, and unwind with some drinks and snacks 🍟 🥤. Let's discuss how we can contribute to the success of your CRISPR-based innovations! #CRISPRMED25 #CRISPR #geneediting #crisprmedicine #sgRNA

A recent study presents a novel approach for synthesizing capped RNA fragments using chemical ligation, overcoming the limitations of traditional enzymatic methods. Eukaryotic mRNAs are characterized by a 5' cap structure, typically consisting of 7-methylguanosine linked to the first transcribed nucleotide through a 5,5-triphosphate bridge. This cap is crucial in various cellular processes, including splicing, intracellular transport, translation initiation, and turnover. While short cap mimics can be synthesized chemically, the preparation of longer capped mRNA analogs has been challenging and typically requires templated enzymatic ligation. Led by researchers from Universität Innsbruck, this study aims to develop a practical, non-templated approach to generate capped RNA fragments with single triazole linkages within the oligo-phosphate backbone. The study explores the use of click chemistry to synthesize capped RNA fragments. The researchers designed and synthesized 3'-alkyne-modified m7G-capped oligoribonucleotides and 5'-azido-modified RNA fragments. These fragments were then ligated using copper-catalyzed azide–alkyne cycloaddition (CuAAC) chemistry, resulting in RNAs with a single triazole linkage within the backbone. The synthesis involved two routes: one using enzymatic N7 methylation and the other using a purely chemical approach. The findings demonstrate the successful production of capped RNA fragments up to 81 nucleotides in length, which are valuable for biochemical, spectroscopic, and structural studies. This method represents a significant advancement towards efficient all-chemical synthesis of mRNAs without the need for in vitro transcription, potentially improving the purity and functionality of synthesized RNA for therapeutic applications. Congratulations to Karolina Bartosik Ronald Micura🎉! Find out more: https://lnkd.in/eUYu7fBp #nucleicacid #mRNA #chemicalbiology #RNAtherapeutics #chemicalligation #RNAsynthesis

Our CTO, David Butler, recently shared insights on our partnership with ReciBioPharm to deliver a unique gene editing drug manufacturing solution in a Q&A with European Pharmaceutical Manufacturer. The strategic partnership leverages Hongene's innovative chemoenzymatic ligation technology, which consistently delivers higher purity sgRNA compared to traditional SPOS methodology. This is coupled with ReciBioPharm’s robust end-to-end CDMO capabilities - located less than an hour from Boston - to streamline the development process, making it efficient and accessible. Providing a one-stop gene editing manufacturing solution greatly simplifies an otherwise highly complex supply chain, mitigates risks, and expedites the delivery of life-changing therapies. We believe that this partnership represents a significant step forward in shaping the future of gene editing therapeutics Read the full article to learn more about how this partnership is redefining the gene editing landscape! https://lnkd.in/eYiPaFep #GeneEditing #GeneTherapy #sgRNA #RNAtherapeutics #CDMO

A recent study investigates the role of the RNA-binding protein ProQ in stabilizing mRNA in Salmonella Typhimurium by inhibiting poly(A) polymerase I (PAPI). The findings reveal that ProQ promotes biofilm formation and affects key virulence-associated traits by protecting specific mRNAs from degradation, highlighting a novel mechanism for RNA stabilization in bacteria. RNA-binding proteins of the ProQ/FinO family are prevalent in various bacterial species and are known to bind to hundreds of different transcripts. ProQ has been shown to stabilize RNA ligands, but the underlying mechanism has been unclear. In Salmonella Typhimurium, ProQ influences several virulence-associated traits, including biofilm formation and intracellular survival, but the direct links between ProQ activity and these phenotypes are not well understood. Led by researchers from Uppsala University, this study aims to elucidate the mechanistic basis of ProQ's role in biofilm formation and RNA stabilization. The researchers constructed various bacterial strains with deletions and complementations of proQ and other relevant genes, used reporter constructs to monitor gene expression, and performed Northern blot and qRT-PCR analyses to quantify mRNA levels. They also used Western blotting to analyze protein levels, EMSA to study RNA-ProQ interactions, and in vitro polyadenylation assays to investigate PAPI activity. The results demonstrate that ProQ is essential for biofilm formation in Salmonella Typhimurium, with its effect being strictly dependent on the sigma factor RpoS. Congratulations to all contributors Sofia Bergman Christopher Birk Erik Holmqvist Find out more: https://lnkd.in/exw6QypV #mRNA #polyA #NucleicAcids

📢 The European Medicines Agency (EMA) has released a draft guideline on the quality aspects of mRNA vaccines. The guideline aims to address specific requirements for the development, manufacture, and control of mRNA vaccines against infectious diseases. The guideline focuses on several key areas: ✅ 𝗔𝗰𝘁𝗶𝘃𝗲 𝗦𝘂𝗯𝘀𝘁𝗮𝗻𝗰𝗲: It outlines the requirements for the mRNA itself, including detailed information on the full mRNA sequence, modifications, and the encoded antigen(s). It also covers the control of starting materials, such as nucleotides and linear DNA templates, which are critical for the manufacturing process. ✅ 𝗖𝗵𝗮𝗿𝗮𝗰𝘁𝗲𝗿𝗶𝘇𝗮𝘁𝗶𝗼𝗻: The guideline emphasizes the need for comprehensive characterization studies throughout the development process, covering both the active substance and the finished product. This includes structural integrity, physicochemical properties, mRNA translation, and impurities. ✅ 𝗖𝗼𝗻𝘁𝗿𝗼𝗹 𝗼𝗳 𝘁𝗵𝗲 𝗔𝗰𝘁𝗶𝘃𝗲 𝗦𝘂𝗯𝘀𝘁𝗮𝗻𝗰𝗲: It specifies the critical quality attributes (CQAs) that should be controlled at release, such as identity, 5’-capping efficiency, poly(A)-tail presence and length, mRNA content, integrity, and functionality. ✅ 𝗙𝗶𝗻𝗶𝘀𝗵𝗲𝗱 𝗣𝗿𝗼𝗱𝘂𝗰𝘁: The guideline provides detailed requirements for the description, composition, pharmaceutical development, and control of the finished product, including LNP attributes, potency, and functionality. ✅ 𝗥𝗲𝗴𝘂𝗹𝗮𝘁𝗼𝗿𝘆 𝗖𝗼𝗻𝘀𝗶𝗱𝗲𝗿𝗮𝘁𝗶𝗼𝗻𝘀: It offers guidance on changes in existing mRNA vaccine strains, bivalent and multivalent vaccines, self-amplifying mRNA vaccines, other delivery systems, and the use of platform technology/prior knowledge approach for new targets. Find out more 👇 #mRNAvaccines #infectiousdiseases #mRNAtherapeutics #vaccinedevelopment