YolTech Therapeutics

Discussions of how AI will revolutionize medicine can sometimes sound like science fiction, but such claims are not new. “Attempts to use technology to enhance doctors’ clinical reasoning skills — or sometimes to replace doctors altogether — are as old as modern medicine itself,” says Adam Rodman, an HMS assistant professor of medicine and a historian of medical epistemology. In 19th-century France, for example, physician Pierre-Charles-Alexandre Louis pioneered the idea of analyzing structured data to glean insights beyond the reach of any individual clinician — an effort that exposed the inefficacy of leeching. In the 1950s, early proponents of epidemiology and biostatistics developed punch card-based computer tools that analyzed data from patient histories to assist with diagnoses. Looking back at these advances is key to putting AI in context, Rodman argues. It makes him optimistic about what could be coming, like “having hundreds or even thousands of AI agents deployed across the health care infrastructure, reading our notes, giving us feedback, recommending personalized education, and even listening in on our encounters with patients, prodding us to ask better questions or consider a diagnosis we might have forgotten.” “It sounds like science fiction,” he adds, “but this future already exists. I’ve used it.” Read more from Rodman in Harvard Medicine magazine: https://bit.ly/3Va86bT

Lipid nanoparticles (#LNPs) have emerged as promising platforms for efficient in vivo mRNA delivery owing to advancements in ionizable lipids. However, maintaining the #thermostability of mRNA/LNP systems remains challenging. While the importance of only a small amount of lipid #impurities on mRNA inactivation is clear, a fundamental solution has not yet been proposed. This study investigates an approach to limit the generation of aldehyde impurities that react with mRNA nucleosides through the chemical engineering of lipids. https://lnkd.in/eF2eb4qA #mRNA #LNP #Ionizable #Lipids #Drugdevelopment #Engineering

🟣 #IonizableLipids, #mRNADelivery, #LNPOptimization | 𝗢𝗽𝘁𝗶𝗺𝗶𝘇𝗮𝘁𝗶𝗼𝗻 𝗼𝗳 𝘁𝗵𝗲 𝗮𝗰𝘁𝗶𝘃𝗶𝘁𝘆 𝗮𝗻𝗱 𝗯𝗶𝗼𝗱𝗲𝗴𝗿𝗮𝗱𝗮𝗯𝗶𝗹𝗶𝘁𝘆 𝗼𝗳 𝗶𝗼𝗻𝗶𝘇𝗮𝗯𝗹𝗲 𝗹𝗶𝗽𝗶𝗱𝘀 𝗳𝗼𝗿 𝗺𝗥𝗡𝗔 𝗱𝗲𝗹𝗶𝘃𝗲𝗿𝘆 𝘃𝗶𝗮 𝗱𝗶𝗿𝗲𝗰𝘁𝗲𝗱 𝗰𝗵𝗲𝗺𝗶𝗰𝗮𝗹 𝗲𝘃𝗼𝗹𝘂𝘁𝗶𝗼𝗻 𝘈 𝘨𝘢𝘮𝘦-𝘤𝘩𝘢𝘯𝘨𝘪𝘯𝘨 𝘢𝘱𝘱𝘳𝘰𝘢𝘤𝘩 𝘵𝘰 𝘳𝘦𝘷𝘰𝘭𝘶𝘵𝘪𝘰𝘯𝘪𝘻𝘦 𝘮𝘙𝘕𝘈 𝘷𝘢𝘤𝘤𝘪𝘯𝘦𝘴 𝘢𝘯𝘥 𝘵𝘩𝘦𝘳𝘢𝘱𝘦𝘶𝘵𝘪𝘤𝘴. 📘 𝗔𝗶𝗺: 🔬 To leverage directed chemical evolution for stepwise optimization of ionizable lipids, enhancing their delivery activity and biodegradability in lipid nanoparticles (LNPs). 📊 𝗞𝗲𝘆 𝗙𝗶𝗻𝗱𝗶𝗻𝗴𝘀: 📈 Five cycles of directed chemical evolution (using amine–aldehyde–alkyne coupling) identified dozens of A3-lipids with comparable or superior delivery activity to benchmark ionizable lipids. 🧬 Structural optimizations improved hepatic mRNA delivery and enhanced intramuscular vaccine efficacy (e.g., against SARS-CoV-2). 📐 Structure–activity relationships for headgroup, ester linkage, and tail were elucidated, accelerating future LNP design. 📌 𝗧𝗮𝗸𝗲 𝗛𝗼𝗺𝗲 𝗠𝗲𝘀𝘀𝗮𝗴𝗲: 🚀 Directed chemical evolution provides a transformative method to optimize ionizable lipids for mRNA delivery, paving the way for safer and more effective LNP-based therapeutics and vaccines. 𝘗𝘶𝘣𝘭𝘪𝘴𝘩𝘦𝘥 𝘰𝘯𝘭𝘪𝘯𝘦: 22 𝘕𝘰𝘷𝘦𝘮𝘣𝘦𝘳 2024, Nature Biomedical Engineering. Check here for more: https://lnkd.in/eQ2BSEMa Thank you to the authors: Xuexiang Han, Mohamad-Gabriel Alameh, @Ying Xu, Rohan Palanki, Rakan El-Mayta, @Garima Dwivedi, Kelsey Swingle, Junchao Xu, Ningqiang Gong, Lulu Xue, Qiangqiang Shi, Il-Chul Yoon, Claude Warzecha, @James Wilson, @Drew Weissman, & Michael J Mitchell. What do you think about this advancement? Drop your thoughts below!

𝗖𝗥𝗜𝗦𝗣𝗥𝗠𝗘𝗗𝟮𝟱: 𝗠𝗲𝗲𝘁 𝘀𝗶𝘅 𝗼𝗳 𝗼𝘂𝗿 𝗶𝗻𝘃𝗶𝘁𝗲𝗱 𝘀𝗽𝗲𝗮𝗸𝗲𝗿𝘀! We are pleased to introduce six of the invited speakers for the 2nd CRISPR Medicine Conference in April 2025 in Copenhagen! First and foremost, we are honoured to announce Virginijus Siksnys as our keynote speaker. A distinguished professor at Vilnius University, Life Sciences Center, Virginijus’ pioneering work has had a major impact in the CRISPR field, laying the foundations for the development of novel genome-editing tools. Patient advocate Jimi Olaghere will share his story about living with sickle cell disease, before and after treatment with the recently approved CRISPR therapy CASGEVY. Annarita Miccio, Director of the Laboratory of Chromatin and Gene Regulation at the Institut Imagine in Paris, will present her team’s efforts to develop gene-editing therapeutic approaches for beta-hemoglobinopathies. Jacob Giehm Mikkelsen is a Professor in Biomedicine at Aarhus University in Denmark. His current research focuses on virus-based protein delivery and cell-vehicle interactions to develop enveloped CRISPR/Cas delivery technologies for the clinic. Alvin L. is a Co-founder and CEO of HuidaGene Therapeutics , which has multiple clinical-stage RNA- and DNA-editing programmes in inherited eye disease, 𝘔𝘌𝘊𝘗2 duplication syndrome and Duchenne muscular dystrophy. Prior to founding HuidaGene, Alvin Luk contributed to global drug approvals, among them LUXTURNA®, the first AAV gene therapy. Zi Jun Emma Wang, Ph.D. is Chief Technology Officer at YolTech Therapeutics, which has three gene-editing programmes in clinical trials. Her focus is on advancing non-viral delivery platforms to support in vivo gene therapy development. See our 𝗳𝘂𝗹𝗹 𝗶𝗻𝘃𝗶𝘁𝗲𝗱 𝘀𝗽𝗲𝗮𝗸𝗲𝗿 𝗹𝗶𝘀𝘁 here: 👉 https://lnkd.in/d7svujCE We are looking forward to your registration! 👉 https://lnkd.in/d2wyXiAH #CRISPRMED25 #crisprmedicinenews #crispr #patientadvocacy

Lipid nanoparticles (#LNPs) employing ionizable lipids are the most advanced technology for delivery of RNA, most notably mRNA, to cells. LNPs represent well-defined core–shell particles with efficient nucleic acid encapsulation, low #immunogenicity and enhanced efficacy. While much is known about the structure and activity of LNPs, less attention is given to the timing of LNP #uptake, #cytosolic transfer and protein expression. However, LNP #kinetics is a key factor determining delivery efficiency. Hence quantitative insight into the multi-cascaded pathway of LNPs is of interest to elucidate the mechanism of delivery. https://lnkd.in/etjCH_ix #mRNA #RNA #LNP #Drugdelivery #Expression #Engineering #ChemicalEngineering #Innovation #MolecularBiology #Chemistry

Efficient delivery of mRNA-#LNPs to specific cell-types remains a major challenge in the widespread application of mRNA #therapeutics. Conventional targeting approaches involve modifying the lipid composition or functionalizing the surface of lipid nanoparticles (LNPs), which complicates manufacturing, alters #nanoparticle size, charge and stealth, impacting their #delivery and #immunogenicity. https://lnkd.in/ev-FV7sa #mRNA #LNP #Drugdelivery #Engineering