Hongene Biotech Corporation

As the calendar winds down on another fruitful year, we are thrilled to close the chapter with remarkable research: 𝗔𝗻 𝗜𝗺𝗽𝗿𝗼𝘃𝗲𝗱 𝗣(𝗩) 𝗧𝗵𝗶𝗼-𝗢𝗹𝗶𝗴𝗼𝗻𝘂𝗰𝗹𝗲𝗼𝘁𝗶𝗱𝗲 𝗦𝘆𝗻𝘁𝗵𝗲𝘀𝗶𝘀 𝗣𝗹𝗮𝘁𝗳𝗼𝗿𝗺🎉! This research presents an improved synthetic platform capable of synthesizing therapeutic oligonucleotides with greater stereocontrol and at a lower cost, marking an important advancement in drug development and chemical synthesis fields. The researchers focused on three key improvements to the P(V) oligonucleotide platform: 1️⃣𝗥𝗲𝗮𝗴𝗲𝗻𝘁 𝗗𝗲𝘃𝗲𝗹𝗼𝗽𝗺𝗲𝗻𝘁: They introduced a more affordable phosphorus-sulfur incorporation reagent, 4-bromothiophenol (Ψᴮʳ), as an alternative to the expensive Pentafluorothiophenol. 2️⃣𝗟𝗶𝗻𝗸𝗲𝗿 𝗦𝘆𝘀𝘁𝗲𝗺: They developed a robust linker system to improve stability during the synthesis process. 3️⃣𝗣𝗿𝗼𝘁𝗲𝗰𝘁𝗶𝗻𝗴 𝗚𝗿𝗼𝘂𝗽𝘀 𝗦𝘁𝘂𝗱𝘆: They conducted a systematic study of nucleobase protecting groups to simplify the synthesis process. ✅𝗠𝗮𝗶𝗻 𝗥𝗲𝘀𝘂𝗹𝘁𝘀: ✔ 𝗖𝗼𝘀𝘁 𝗥𝗲𝗱𝘂𝗰𝘁𝗶𝗼𝗻: The new reagent, Ψᴮʳ, was found to be competent in preparing nucleoside monomers and reduced the cost of the leaving group by 10-fold. ✔ 𝗟𝗶𝗻𝗸𝗲𝗿 𝗦𝘁𝗮𝗯𝗶𝗹𝗶𝘁𝘆: A Sar-Glu-based linker was identified as the most stable under P(V) coupling conditions, showing a 94% recovery after 120 coupling cycles. ✔ 𝗣𝗿𝗼𝘁𝗲𝗰𝘁𝗶𝗻𝗴 𝗚𝗿𝗼𝘂𝗽 𝗖𝗼𝗺𝗽𝗮𝘁𝗶𝗯𝗶𝗹𝗶𝘁𝘆: The study found that certain protecting groups, such as Pya, dma, and nonprotected bases, were compatible with SPOS, while Benzoyl groups were not. They also identified suitable protecting groups for each base, allowing for the synthesis of a full-length, mixed-base oligonucleotide with similar yield and quality to those made with previously published monomers. These improvements not only streamline the adoption of the P(V)-platform for therapeutic oligonucleotide synthesis but also make it more accessible for industrial and academic applications. The optimized reagents, linkers, and protecting groups contribute to a more efficient and cost-effective synthesis process, potentially accelerating the discovery and development of new therapeutic oligonucleotides！ Congratulations to all contributors🎉! Molhm Nassir Luca Gherardi Scripps Research Richard Redman Elsie Biotechnologies Our Hongene team is proud to be part of this remarkable work 👏 ! David Butler Feng Yao Yang Yang #oligonucleotide #RNAtherapeutics #SPOS

#excitingnews The European Commission approved KOSTAIVE® (ARCT-154), the first self-amplifying #mRNA #COVID19 vaccine developed by CSL and Arcturus Therapeutics! This is a breakthrough in vaccine technology, offering superior immunogenicity and antibody persistence for up to 12 months post-vaccination compared to conventional mRNA vaccines.  𝗞𝗲𝘆 𝗵𝗶𝗴𝗵𝗹𝗶𝗴𝗵𝘁𝘀 1️⃣ 𝗙𝗶𝗿𝘀𝘁 𝗼𝗳 𝗶𝘁𝘀 𝗸𝗶𝗻𝗱: KOSTAIVE is the first self-amplifying mRNA COVID-19 vaccine to receive European Commission approval. 🚀 𝗦𝘂𝗽𝗲𝗿𝗶𝗼𝗿 𝗽𝗿𝗼𝘁𝗲𝗰𝘁𝗶𝗼𝗻: Clinical trials showed higher immunogenicity and long-lasting antibody persistence against multiple SARS-CoV-2 strains. 💡 𝗜𝗻𝗻𝗼𝘃𝗮𝘁𝗶𝘃𝗲 𝘁𝗲𝗰𝗵𝗻𝗼𝗹𝗼𝗴𝘆: Unlike standard mRNA vaccines, self-amplifying mRNA vaccines instruct the body to make more mRNA and protein to boost the #immuneresponse. Congratulations to the teams at CSL and Arcturus Therapeutics on this remarkable achievement! 🎉 Find out more: https://lnkd.in/dqinSB7F #selfamplifyingmRNA #COVID19Vaccine #vaccinedevelopment

A new study presents an innovative analytical method for characterizing and quantifying phosphorothioate (PS) modifications in single-guide RNA (sgRNA) used in CRISPR/Cas9 genome editing. The study addresses the challenge of distinguishing and quantifying PS-induced isomers in complex mixtures, offering a significant advancement in the analytical capabilities for sgRNA modifications! CRISPR/Cas9 technology has revolutionized genetic research and therapy by enabling precise and efficient DNA editing. sgRNA is crucial in directing the Cas9 enzyme to specific DNA sequences. However, sgRNA is often vulnerable to degradation by cytosolic exonucleases, which can compromise gene-editing precision and efficiency. To enhance sgRNA stability, phosphorothioate (PS) modifications are frequently introduced into the sgRNA backbone. These modifications can create complex mixtures of constitutional and stereoisomers, posing significant challenges for reliable identification and quantification using current analytical techniques. Researchers from Regeneron developed a novel methodology combining endonuclease digestion of sgRNA with ion pairing reversed-phase liquid chromatography (IPRP-LC) and cyclic ion mobility mass spectrometry (cIMS). This approach fully separates PS-induced isomers in complex mixtures. The relative abundance of each isomer was quantified using a two-step method, extracting ion abundance from LC/MS ion chromatograms and LC/cIMS two-dimensional ion mobiligrams. The method was thoroughly evaluated for sensitivity, precision, dynamic range, repeatability, and accuracy. Additionally, the study investigated the kinetics of PS to phosphodiester (PO) impurities under oxidative stress conditions, providing insights into PS stability at single-residue resolution. The method exhibited excellent sensitivity, with a limit of detection close to 9.7 fmol, and a wide dynamic range (0.2−100%). The relative standard deviations (RSD) were low, indicating high repeatability, and the experimental values closely matched expected values, demonstrating high accuracy. The method was applied to study the oxidation kinetics of PS modifications in sgRNA under stress conditions, revealing that terminal PS groups are oxidized more rapidly than internal ones. This finding highlights the non-random nature of PS oxidation and provides valuable insights into PS stability. The developed method significantly enhances the analytical capabilities for characterizing PS modifications in sgRNA, supporting biomedical research, development, and production of oligonucleotide therapeutics. Congratulations to all contributors 👏 ! Find out more: https://lnkd.in/eui3xt4h #Oligonucleotides #RNAtherapeutics #sgRNA #crispr #geneediting

Excited to announce that the Hongene team is gearing up to participate in Tides Asia 2025!   We'll be at 𝗯𝗼𝗼𝘁𝗵 #4, ready to connect with experts in the oligonucleotide, peptide, mRNA, and genome editing and delivery fields.   We're eager to explore new collaboration opportunities and showcase our extensive experience and capabilities in oligonucleotide and mRNA raw materials and CDMO services.   Join us at Tides Asia 2025, and let's work together to drive your projects to success! #TidesAsia #Hongene #oligonucleotide #mRNA #nucleicacid #CDMO

Researchers from Chroma Medicine explore the development and application of an #epigeneticeditor designed to durably reduce PCSK9 levels, thereby lowering low-density lipoprotein cholesterol (LDL-C) through targeted DNA methylation. The study demonstrates the potential of this approach in both in vitro and in vivo models, highlighting its therapeutic potential for #hypercholesterolemia! #Epigenetic editing offers a promising approach to modulating #geneexpression by inducing #DNAmethylation without altering the underlying DNA sequence. This method can silence disease-causing genes durably and safely. #PCSK9 is a key regulator of LDL-C levels, and its inhibition has been shown to reduce cardiovascular risk. Traditional methods of PCSK9 inhibition, such as monoclonal antibodies and RNA interference, require chronic dosing. This latest study aims to develop a single-dose epigenetic editor that can durably reduce PCSK9 levels and LDL-C by inducing methylation at the PCSK9 locus. Led by Frederic Tremblay, the team designed an epigenetic editor (EE) comprising DNMT3A, DNMT3L, and a KRAB transcriptional repressor domain fused to catalytically inactive Cas9 (dCas9). They performed a gRNA screen to identify guides that efficiently induce methylation at the PCSK9 locus. The top-performing gRNAs were formulated into lipid nanoparticles (#LNPs) and tested in primary human hepatocytes (PHHs) and transgenic mice expressing human PCSK9. The study also evaluated the specificity of the EE using RNA sequencing and methylation assays. Additionally, the reversibility of the epigenetic editing was tested using a demethylating agent in mice. Finally, the efficacy and safety of the EE were assessed in cynomolgus monkeys. The study demonstrated that a single administration of the EE in transgenic mice achieved near-complete silencing of PCSK9, which was durable for at least one year and maintained after liver regeneration. The treatment also significantly reduced LDL-C levels. In cynomolgus monkeys, a single infusion of the EE led to a robust and durable reduction in circulating PCSK9 and LDL-C levels, with minimal off-target effects. The findings highlight the therapeutic potential of #epigeneticediting for hypercholesterolemia, offering a one-and-done treatment approach that could disrupt the current paradigm of chronic therapy. Future work will focus on further preclinical evaluation and optimization of the EE for clinical translation. Congratulations to all contributors🎉! Find out more: https://lnkd.in/eC55NcV6

Researchers from McGill University developed innovative methods to enhance the stability and efficacy of self-assembled spherical nucleic acids (SNAs), improving their potential for therapeutic applications! Oligonucleotide therapeutics, including antisense oligonucleotides (#ASOs) and small interfering RNA (#siRNA), hold significant promise for modulating the expression of disease-associated proteins. However, their application is hindered by challenges such as nuclease degradation, poor cellular uptake, and unspecific targeting. #SNAs have emerged as versatile tools for #nucleicacid delivery, offering improved resistance to degradation and enhanced cellular uptake. Despite these advantages, self-assembled SNAs can be fragile, often disassembling in the presence of serum proteins. This novel study introduced two methods of covalent crosslinking via UV irradiation—thymine photodimerization and disulfide crosslinking—to enhance SNA stability. The researchers synthesized DNA amphiphiles and self-assembled them into SNAs. They introduced thymine repeats and disulfide bonds at the interface of the SNA for crosslinking. Two UV irradiation methods were employed: UVB (290–320 nm) for thymine dimerization and UVA (320–400 nm) for disulfide crosslinking. The crosslinking efficiency was assessed using denaturing polyacrylamide gel electrophoresis (PAGE). The stability of crosslinked SNAs against human serum albumin (HSA) binding was evaluated using size exclusion chromatography (SEC). Cellular uptake was measured using flow cytometry, and gene silencing efficacy was tested in HeLa cells. The findings demonstrate that these crosslinked SNAs exhibit unprecedentedly high crosslinking yields, enhanced stability against albumin binding, and significantly improved cellular uptake—up to four. This research paves the way for further optimization and exploration of SNAs in pre-clinical and in vivo studies, offering promising avenues for advancing #nucleicacidtherapeutic delivery! Congratulations to all contributors🎉! Sepideh Kaviani Haochen Bai Masad J. Damha, PhD, FCIC Quentin Laurent Hanadi Sleiman Find out more: https://lnkd.in/ea2fYUKp #oligonucleotide #RNAtherapeutics #drugdelivery

A recent article delves into the structure-activity relationship of antibody-oligonucleotide conjugates (AOCs), providing a comprehensive understanding of how the design of AOCs can influence their pharmacokinetic properties and tissue-targeting capabilities, ultimately advancing the field of RNA therapeutics. AOCs represent a promising therapeutic strategy for delivering siRNAs to target tissues outside the liver. siRNAs are potent agents for gene silencing but face challenges such as instability, off-target effects, and inefficient delivery. Antibodies, with their high specificity and ability to target various tissues, can enhance siRNA delivery when conjugated. However, optimizing these conjugates requires a comprehensive understanding of structure−activity relationships (SAR) to improve their stability, pharmacokinetics, and efficacy. Researchers from Avidity Biosciences, Inc. evaluated various factors affecting the performance of antibody−siRNA conjugates, including antibody isotype, siRNA chemistry, linkers, conjugation sites, and drug-to-antibody ratios (DARs), on the pharmacokinetics (PK), delivery, and bioactivity of these conjugates. The study found that: 💡 𝗢𝗽𝘁𝗶𝗺𝗮𝗹 𝗖𝗼𝗻𝗷𝘂𝗴𝗮𝘁𝗶𝗼𝗻 𝗦𝘁𝗿𝗮𝘁𝗲𝗴𝘆: Cysteine conjugation and a DAR of 1 were optimal for AOC stability and efficacy. 💡 𝗟𝗶𝗻𝗸𝗲𝗿 𝗜𝗺𝗽𝗮𝗰𝘁: Cleavable linkers with increased steric hindrance demonstrated better plasma stability compared to less hindered linkers; Noncleavable linkers showed no significant differences in plasma exposure or target mRNA KD in rapidly internalized AOCs. 💡 𝘀𝗶𝗥𝗡𝗔 𝗠𝗼𝗱𝗶𝗳𝗶𝗰𝗮𝘁𝗶𝗼𝗻𝘀: siRNA chemical modifications, such as locked nucleic acids (LNA) and unlocked nucleic acids (UNA), enhanced stability and duration of action in vivo. 💡 𝗣𝗘𝗚𝘆𝗹𝗮𝘁𝗶𝗼𝗻: The addition of polyethylene glycol (PEG) to the conjugate improved tissue delivery and gene KD efficacy. 💡 𝗖𝗼𝗻𝗷𝘂𝗴𝗮𝘁𝗶𝗼𝗻 𝗦𝗶𝘁𝗲𝘀: Conjugation at the 5′ end of the siRNA sense strand was more effective than internal positions (e.g., positions 8 or 14) in terms of target mRNA KD. 💡 𝗔𝗻𝘁𝗶𝗯𝗼𝗱𝘆 𝗜𝘀𝗼𝘁𝘆𝗽𝗲 𝗮𝗻𝗱 𝗗𝗔𝗥: Different antibody isotypes (e.g., hIgG1, hIgG2, hIgG4) required specific conjugation conditions to maximize DAR1 yield. 💡 𝗚𝗲𝗻𝗲𝗿𝗮𝗹 𝗔𝗽𝗽𝗹𝗶𝗰𝗮𝗯𝗶𝗹𝗶𝘁𝘆: The AOC platform is flexible and can be applied to various antibodies and siRNA targets. This study underscores the critical role of structure-activity relationships in optimizing AOCs for enhanced therapeutic outcomes. By addressing key challenges in oligonucleotide delivery, it advances the potential of AOCs as powerful tools for precision medicine, offering hope for patients with previously untreatable conditions. Congratulations to all contributors🎉! Michael Cochran Venkata Doppalapudi Find out more here: https://lnkd.in/dz-vAUNB #AOC #siRNA #RNAi #RNAtherapeutics #drugdevelopment #drugdelivery #antibody #oligonucleotides

📑 The European Medicines Agency (EMA) has released 𝗘𝗠𝗔 𝟮𝟬𝟮𝟰 𝗛𝘂𝗺𝗮𝗻 𝗠𝗲𝗱𝗶𝗰𝗶𝗻𝗲𝘀 𝗥𝗲𝗽𝗼𝗿𝘁, highlighting significant advancements in the field of #pharmaceutical. Key takeaways: 💊 𝗡𝗲𝘄 𝗠𝗲𝗱𝗶𝗰𝗶𝗻𝗲𝘀 𝗔𝘂𝘁𝗵𝗼𝗿𝗶𝘇𝗲𝗱: A total of 114 positive opinions were issued for marketing authorizations, with 46 of these being for new active substances. Notably, 15 of the approved medicines are designated as orphan drugs, targeting rare diseases that often lack treatment options. Among these approvals, there is a strong focus on oncology, with many cancer treatments gaining approval, alongside advancements in other fields such as neurology, pneumology/allergology, and vaccines. 🎖️ 𝗧𝗵𝗲𝗿𝗮𝗽𝗲𝘂𝘁𝗶𝗰 𝗕𝗿𝗲𝗮𝗸𝘁𝗵𝗿𝗼𝘂𝗴𝗵𝘀: Notable approvals include Welireg for treating tumors associated with von Hippel-Lindau disease, Winrevair for pulmonary arterial hypertension, and Emcitate for peripheral thyrotoxicosis in Allan-Herndon-Dudley syndrome. These medicines address previously unmet medical needs. ❗ 𝗣𝘂𝗯𝗹𝗶𝗰 𝗛𝗲𝗮𝗹𝘁𝗵 𝗘𝗺𝗲𝗿𝗴𝗲𝗻𝗰𝗶𝗲𝘀: In response to the mpox pandemic, the EMA expedited the approval of treatments and vaccines. The smallpox and mpox vaccine Imvanex was recommended for use in adolescents aged 12 to 17. Its EMA assessment was crucial for the WHO's prequalification approval, facilitating access in communities in need. 🚀 𝗔𝗰𝗰𝗲𝗹𝗲𝗿𝗮𝘁𝗲𝗱 𝗔𝘀𝘀𝗲𝘀𝘀𝗺𝗲𝗻𝘁𝘀 𝗮𝗻𝗱 𝗣𝗥𝗜𝗠𝗘: Three medicines benefited from accelerated assessments, and six PRIME-designated medicines were recommended for approval. PRIME aims to optimize data generation and enable faster assessments for promising medicines targeting unmet needs. ✅ 𝗖𝗼𝗻𝗱𝗶𝘁𝗶𝗼𝗻𝗮𝗹 𝗮𝗻𝗱 𝗘𝘅𝗰𝗲𝗽𝘁𝗶𝗼𝗻𝗮𝗹 𝗔𝗽𝗽𝗿𝗼𝘃𝗮𝗹𝘀: Eight medicines received conditional marketing authorizations, allowing early access based on less complete clinical data. Four medicines were authorized under exceptional circumstances, providing treatment options when standard approval is not feasible. 🧪 𝗥𝗮𝗿𝗲 𝗗𝗶𝘀𝗲𝗮𝘀𝗲𝘀: The EU's orphan medicines framework continues to encourage development, with 15 medicines confirmed for orphan designation by year-end. These include treatments for various rare cancers, genetic disorders, and infectious diseases. 🔎 𝗦𝗮𝗳𝗲𝘁𝘆 𝗮𝗻𝗱 𝗠𝗼𝗻𝗶𝘁𝗼𝗿𝗶𝗻𝗴: Post-authorization, the EMA and EU Member States continuously monitor medicine quality and safety. New safety advice was issued for several medicines, including CAR T-cell therapies, fluoroquinolones, and GLP-1 receptor agonists, ensuring their safe and effective use. Find out more below 👇 #EMA #drugdevelopment #medicines

#breakingnews Arrowhead Pharmaceuticals just announced that the FDA has accepted the New Drug Application (NDA) for investigational plozasiran to treat familial chylomicronemia syndrome (#FCS), a severe and rare genetic disease. The clinical basis of the NDA submission is comprised of the positive findings in the Phase 3 PALISADE study with supportive confirmatory evidence from the Phase 2 clinical studies of the SUMMIT Program. PALISADE successfully met its primary endpoint and all multiplicity-controlled key secondary endpoints, including statistically significant reductions in triglycerides (TGs), apolipoprotein C-III (APOC3), and the incidence of acute pancreatitis (AP). FCS is a severe and #raredisease often caused by various monogenic mutations. FCS leads to extremely high triglyceride (TG) levels, typically over 880 mg/dL. Such severe elevations can lead to various serious signs and symptoms including acute and potentially fatal pancreatitis, chronic abdominal pain, diabetes, hepatic steatosis, and cognitive issues. Currently, there are limited therapeutic options to treat FCS adequately. Plozasiran, previously called ARO-APOC3, is a first-in-class investigational RNA interference (#RNAi) therapeutic designed to reduce the production of apolipoprotein C-III (APOC3) which is a component of triglyceride rich lipoproteins (TRLs) and a key regulator of triglyceride metabolism. APOC3 increases triglyceride levels in the blood by inhibiting breakdown of TRLs by lipoprotein lipase and uptake of TRL remnants by hepatic receptors in the liver. The goal of treatment with plozasiran is to reduce the level of APOC3, thereby reducing triglycerides and restoring lipids to more normal levels. Find out more details below 👇 ! #RNAtherapeutics #geneticdisease #GalNAc #FDA #NDA

#Musculardystrophies (MD) are a group of genetic disorders characterized by progressive muscle weakness and degeneration. The diseases can vary in severity, age of onset, and specific muscles affected. Duchenne muscular dystrophy (DMD) is the most common form. Current treatments focus on managing symptoms and slowing disease progression but do not cure the underlying genetic defects. A recent review led by scientists from Tel Aviv University provides a comprehensive overview of the current state of #genedelivery technologies for muscular dystrophies. It underscores the challenges and opportunities in developing effective delivery systems, guiding future research directions. Muscle-Targeting Gene Delivery Strategies 1️⃣ 𝗩𝗶𝗿𝗮𝗹 𝗩𝗲𝗰𝘁𝗼𝗿-𝗕𝗮𝘀𝗲𝗱 𝗗𝗲𝗹𝗶𝘃𝗲𝗿𝘆: Adeno-associated viruses (AAVs) are widely used due to their high transduction efficiency and cardiac tropism. However, they face limitations such as limited cargo capacity and pre-existing immunity in patients. Lentiviruses offer advantages like long-term expression and larger packaging capacity but are limited by unpredictable integration sites and immune responses. 2️⃣ 𝗡𝗼𝗻-𝗩𝗶𝗿𝗮𝗹 𝗗𝗲𝗹𝗶𝘃𝗲𝗿𝘆 𝗠𝗲𝘁𝗵𝗼𝗱𝘀: Lipid nanoparticles (LNPs) have emerged as a promising non-viral alternative, offering the possibility of re-administration and higher packaging capacity. However, they face challenges such as low muscle transduction efficiency and liver tropism. Other non-viral approaches include extracellular vesicles (EVs) and polymer nanoparticles (PNPs), which are still under development for muscle-specific delivery. 3️⃣ 𝗔𝘀𝘀𝗶𝘀𝘁𝗶𝘃𝗲 𝗧𝗲𝗰𝗵𝗻𝗼𝗹𝗼𝗴𝗶𝗲𝘀: Techniques like electro-enhanced plasmid transfer and isolated limb vein injection are explored to improve gene delivery efficiency, particularly to distal muscles. These methods aim to enhance the effectiveness of gene therapy by overcoming barriers such as muscle fibrosis and liver clearance. While they could be invasive, technically challenging, and have variable efficacy depending on the specific method and muscle group. 💡Core Points This review provides a comprehensive overview of the current state of gene delivery technologies for muscular dystrophies. It underscores the challenges and opportunities in developing effective delivery systems, guiding future research directions. By highlighting the strengths and weaknesses of various delivery methods, the review aids in the development of more efficient gene therapies, potentially improving the quality of life for patients with muscular dystrophies. Congratulations to all contributors🎉! Yulia Chulanova Dor Breier Dan Peer Explore more: https://lnkd.in/eEv5a9_n #genedelivery #genetherapy #geneediting #AAV #LNP #geneticmedicines