Precision Medicine Online’s Post

🔬 Exciting Advances in RNA Therapeutics! 🧬 As we continue to witness the incredible potential of RNA-based treatments, particularly following their pivotal role in COVID-19 vaccine development, it's clear that the future of medicine is being shaped right before our eyes. A recent article from Promega Connections dives into the world of RNA therapeutics and the critical role of custom in vitro transcription reagents in this rapidly evolving field. The journey from the lab bench to large-scale production is laden with challenges, especially adhering to current Good Manufacturing Practices (cGMPs). The transition from research-use-only RNA to cGMP-compliant RNA suitable for clinical trials is not just a step but a giant leap in ensuring the quality and safety of these potential life-saving therapies. In a notable collaboration with Duke University, Promega has been at the forefront, developing customizable cGMP-compliant in vitro transcription raw materials. This initiative was catalyzed by the need for high-quality, scalable RNA production during the pandemic, and Promega's expertise played a pivotal role in supporting RNA vaccine research and development. This collaboration not only accelerated COVID-19 vaccine development but also opened new avenues for RNA therapeutics in fighting diseases like HIV, influenza, Zika, RSV, and even cancer. Promega's commitment to innovation and quality is evident as they now offer custom formulations of cGMP-grade in vitro transcription reagents. This is a game changer for researchers and manufacturers, bridging the gap between early research and the delivery of safe, effective RNA therapeutics. 🌐 Read the full article to understand how Promega is revolutionizing RNA therapeutic manufacturing and what this means for the future of healthcare. https://lnkd.in/gmiWTDXJ #RNAtherapeutics #Biotechnology #InnovationInHealthcare #Promega #LifeSciences #VaccineDevelopment #cGMP #ClinicalResearch

Recent advances in nanoparticulate RNA delivery systems Nanoparticle-based RNA delivery has shown great progress in recent years with the approval of two mRNA vaccines for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and a liver-targeted siRNA therapy. Here, we discuss the preclinical and clinical advancement of new generations of RNA delivery therapies along multiple axes. Improvements in cargo design such as RNA circularization and data-driven untranslated region optimization can drive better mRNA expression. New materials discovery research has driven improved delivery to extrahepatic targets such as the lung and splenic immune cells, which could lead to pulmonary gene therapy and better cancer vaccines, respectively. Other organs and even specific cell types can be targeted for delivery via conjugation of small molecule ligands, antibodies, or peptides to RNA delivery nanoparticles. Moreover, the immune response to any RNA delivery nanoparticle plays a crucial role in determining efficacy. Targeting increased immunogenicity without induction of reactogenic side effects is crucial for vaccines, while minimization of immune response is important for gene therapies. New developments have addressed each of these priorities. Last, we discuss the range of RNA delivery clinical trials targeting diverse organs, cell types, and diseases and suggest some key advances that may play a role in the next wave of therapies. https://lnkd.in/eFcRVFbi

RNA molecules have emerged as promising clinical therapeutics due to their ability to target “undruggable” proteins or molecules with high precision and minimal side effects. Nevertheless, the primary challenge in RNA therapeutics lies in rapid degradation and clearance from systemic circulation, the inability to traverse cell membranes, and the efficient intracellular delivery of bioactive RNA molecules. In this review, we explore the implications of RNAs in diseases and provide a chronological overview of the development of RNA therapeutics. Additionally, we summarize the technological advances in RNA-screening design, encompassing various RNA databases and design platforms. The paper then presents an update on FDA-approved RNA therapeutics and those currently undergoing clinical trials for various diseases, with a specific emphasis on RNA medicine and RNA vaccines.

Circular RNA (circRNA) is a single-stranded #RNA that uses covalent bonds to joing the 3' and 5' ends together. CircRNA can help overcome a lot of the issues experienced with stability, cold chain storage, and manufacturing. It also may improve R. Alexander Wesselhoeft, PhD, director of RNA Therapeutics at the Gene and Cell Therapy Institute, Mass General Brigham, says it is still early days with circRNA, but based on preclinical research, these candidates could be even better than mRNA therapies. This includes #AAV - because you can give a smaller dose than previously seen in other therapeutics. https://lnkd.in/dHgyjr_h #circRNA #cgt ##celltherapy #genetherapy #molecularbiology #mRNA #LNP #research #innovation #scientists

IV-formulated, non-lipid RNA delivery is more than just a breakthrough for CNS—it's a versatile RNA delivery platform capable of unlocking systemic therapeutic opportunities beyond the reach of lipid nanoparticles and viral vectors. Precise Delivery: Systemic mRNA or RNAi therapeutics are delivered directly to challenging disease sites throughout the body, including tissues previously considered "undruggable." Our BDDS platform payloading includes ASO, siRNA, and up to 4900 NT mRNA. Innovative Approach: Our non-lipid delivery system circumvents the limitations of immunogenicity and tissue targeting. A New Route: Pave the way for peripheral delivery therapies that demand precision. Why Partner with Us? Our platform can accelerate your systemic RNA-based programs, targeting areas from cardiovascular diseases to rare genetic disorders and delivering superior patient outcomes. Proven Efficacy: Our preclinical data demonstrates targeted biodistribution across multiple organs in rodent and non-human primate models. Collaborative Innovation: Transform your ambitious therapeutic goals into reality with our novel approach. Contact BIORCHESTRA Co., Ltd. to learn how our BDDS technology can be tailored to your specific targets of interest and deliver the next wave of RNA medicines that could redefine standards of care.

1. The amount of RNA therapeutics approved for Phase 1 clinical trials globally is increasing at a steady rate; this is due to advancement in RNA technologies, interest in RNA therapeutics, innovations in drug delivery systems, and clear guidelines established for the development and approval of RNA therapeutics by the FDA and EMA. 2. Due to the above factors, the number in 2024 is set to eclipse that in 2023 by a substantial margin. 3. Lipid nanoparticles continue to be a popular choice of drug delivery system due to the success of COVID-19 mRNA vaccines (Note: a large portion of "Other" is undisclosed). 4. Most RNA therapeutic types are increasing in numbers. Interestingly, antisense oligonucleotides (ASOs), seen a dip shortly after the pandemic but have since maintained relevancy. 5. In 2024, guide RNA make up almost a third of RNA therapeutics approved for Phase 1 clinical trials, highlighting the rise of gene editing technologies such as CRISPR-Cas9 in treating genetic disorders, cancers, and infectious diseases. Data obtained from Beacon Intelligence using the "RNA therapeutics" and "Trial Start Date" parameters. #RNA #RNAtherapeutics #mRNA #mrnatherapeutics #mrnavaccines #LNP #lipidnanoparticles #liposome #mrnalnp #drugdelivery #crispr #crisprcas9 #geneediting #genetherapy #helixbiotech

The Beacon RNA team identified 500 new RNA drugs that have entered pipelines in 2024 so far – tracking nicely to surpass last year’s growth (880 across the whole of 2023). We continue to see increased complexity into new modalities & areas but also additional competition in the same modalities for a given disease or target. Some hot areas in RNA development: ·      Antibody-oligonucleotide conjugates – strong data from Avidity Biosciences & Dyne Therapeutics has sparked new interest in using antibody targeting, alongside other novel approaches for peptide conjugates & other ligands to support extra-hepatic delivery ·      Novel editing mechanisms – epigenome & RNA editing raised attention at ASGCT as people look to expand their editing toolkit for different gene/mutations ·      Innovative mRNA therapeutics – High interest & activity in in-vivo mRNA cell therapies with new data at AACR & ASGCT. 50% of new mRNA vaccines are for oncology indications & increased activity for protein replacement & antibody production mechanisms. Some interesting mRNA therapies encoding cytokines & multi-specifics antibodies now emerging. Looking forward to seeing the data readouts for these newer areas throughout the rest of the year! #RNA 

Explore the biopharma technologies and techniques that will help you advance the development of the latest drug modalities, including next-generation antibody therapeutics and cell and gene therapies. #Biopharmaceuticals #CellandGeneTherapy #Antibodytherapeutics

Boehringer Ingelheim signs $1.3B deal with RNA biotech Ochre Bio to team up against MASH Boehringer Ingelheim is making yet another bet that RNA therapies hold the key to treating metabolic-associated steatohepatitis (MASH). The German drugmaker is paying British biotech Ochre Bio $35 million in upfront and near-term research-based milestone payments to investigate “multiple targets” for chronic liver disease. Top of the list of indications will be MASH, previously known as nonalcoholic steatohepatitis (NASH). Should any of the targets in the “multi-year” collaboration prove fruitful, Ochre is also in line for various clinical, regulatory and commercial milestones as well as tiered royalties, which add up to a deal value north of $1 billion. capabilities in order to halt or reverse chronic liver diseases. It’s far from the first time Boehringer has played in this space—the pharma kicked off the year signing a $2 billion biobucks deal with Suzhou Ribo Life Science and Ribocure Pharmaceuticals to see whether their RNAi drug platform that targets disease-causing genes specifically in liver cells could complement Boehringer’s own MASH expertise. Six years earlier, Boehringer penned back-to-back partnerships with Dicerna Pharmaceuticals and MiNA Therapeutics covering the use of siRNA and small activating RNA to treat MASH. https://lnkd.in/euBU-DNf