Arnaud Delobel, Ph.D.’s Post

🔍 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. Whether you're a seasoned researcher or new to the field of RNA therapeutics, this review offers a comprehensive look at the potential and challenges associated with LNPs, making it a crucial read for anyone involved in the development of new treatments. Attached is the full publication for those interested in a more detailed read. 🎯 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. #Nanomedicine #RNATherapeutics #LipidNanoparticles #GeneTherapy #Biotechnology #DrugDelivery #mRNA #InnovativeMedicine #HealthcareInnovation #ScientificResearch Yutian Ma Shiyao Li Xin Lin & Yupeng Chen

Sickle cell disease (SCD) is a genetic blood disorder characterized by abnormal hemoglobin, the protein in red blood cells that carries oxygen throughout the body. This genetic mutation causes red blood cells to become rigid and assume a sickle-like shape under certain conditions, such as low oxygen levels or dehydration. These abnormal sickle-shaped cells can get stuck in small blood vessels, leading to various complications. Research into sickle cell disease is ongoing, with a focus on developing new treatments and improving outcomes for individuals with the condition. Clinical trials play a crucial role in testing the safety and efficacy of new therapies, including gene therapy, gene editing techniques like CRISPR-Cas9, and novel medications targeting specific aspects of the disease. Submissions are Open! You may submit case report, clinical image, clinical trial, research article, short review, commentary, letter to the editor. For more updates follow: https://lnkd.in/dbe9q2eC For any queries contact: Clinicalcasereports@maplejournal.com Source: Internet #clinicaltrials #clinicalresearch #sicklecellanaemia #geneticdisorder

🌟 Company Spotlight: Ascidian Therapeutics 🌟 Led by Michael Ehlers At the forefront of #RNA therapeutics, Ascidian Therapeutics is revolutionizing the treatment of genetic diseases. Inspired by the unique biology of sea squirts (ascidians), the company has developed a pioneering RNA exon editing platform that offers a novel approach to gene therapy. 🔬 Innovative Technology: Ascidian’s platform enables precise post-transcriptional editing of RNA, allowing for the correction of genetic mutations at the exon level. This technology ensures the production of full-length, functional proteins, addressing diseases that current gene editing technologies cannot. 🧬 Clinical Impact: The company’s lead program, #ACDN-01, targets Stargardt disease and other #ABCA4 #retinopathies. Currently in Phase 1/2 clinical trials, this program aims to provide a one-time treatment that could significantly improve patients’ lives. 🤝 Strategic Partnerships: Ascidian has also entered a groundbreaking collaboration with Roche to develop RNA exon editing therapeutics for neurological diseases. This partnership combines Ascidian’s innovative technology with Roche’s advanced #CNS delivery capabilities. 🌍 Vision: By harnessing the power of RNA biology, Ascidian Therapeutics is committed to delivering life-changing treatments to patients worldwide. Their work represents a significant leap forward in the field of genetic medicine. #Fierce15 #FiercePharma #Ascidian #Roche #CRO #ContractResearch #clinicaldata

Out this morning, but behind a STAT+ paywall, a patient death in Beam's CRISPR trial for SCD. + A BEAM patient died in a CRISPR Sickle Cell Treatment study. The preliminary conclusion is that the death was the result of respiratory failure likely caused by the conditioning regimen necessary prior to BEAM-101 treatment. + The patient died four months after receiving BEAM-101. + The FDA is aware of the death and the Beam study is continuing without changes. + The death was revealed in ASH abstracts, released today at 9 am to the public. + Editorial Note - the missing part of this story is how Beam is so confident a death 4 months after infusion stemmed from the conditioning regimen v. BEAM-101, but obviously FDA shares this confidence so we’re likely to hear more soon. + The patient patient was one of six participants in the trial. While Vertex has Casgevy CRISPR therapy approved for SCD, Beam is targeting reduction in organ damage which contributes to early death in the dieases. + Busulfan is the conditioning regimen that both Beam and Vertex (and several other ex vivo gene therapies) share. + Editorial Note: Busulfan is reliable but brutal – we’ve known this. Vertex has been vocal about searching for alternatives, as have other companies. Readout Loud did an excellent podcast on this topic several years ago. Busulfan is a beast - but a reliable, necessary, imporant one. #beam #crispr #sicklecelldisease #genetherapy Original article here - https://lnkd.in/ea_E4X4Y

Teaser for our upcoming 7 part series "Fixing the Potholes in Cell and Gene Therapy", when live in October find it here: https://lnkd.in/eg5E_6A8 , this snippet is from chapter 6 Series panelist are Sean Hart, PhD LumaCyte Fabian Gerlinghaus Cellares Peter Marks FDA and Fyodor Urnov Innovative Genomics Institute & University of California, Berkeley . This teaser focuses on predictive analytics to guide manufacturing and improve product consistency, alongside prescriptive analytics to adjust for donor cell variability. Chapter one: Introductions, Success and Challenges (Potholes) in Cell and Gene Therapy: automation, regulatory certainty, and standardizing manufacture processes such as vector constructs or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) steps. Chapter two: Standardization leading to CGT therapies becoming a standard of care. Importance to outcomes of high-quality starting materials, to reducing batch-to-batch quality, and the possibilities of allogeneic chimeric antigen receptor therapy (CAR-T) successes. Chapter three: Popular new delivery vectors, and some not fully appreciated like Non-AAV parvoviruses or Herpes Simplex virus. Are we in a transition state, where there is a growing a trend away from Viral Vectors? How do we best regulate CRISPR? Chapter four: Repairing nucleotide abnormalities for rare disease populations as pivotal proving grounds for transformative therapies. Chapter five: Looking ahead 5-10 years for in vivo practice. Combined platform and modalities marriages, to bring CGT up to first relapse or consolidation therapies. Chapter six: Optimizing analytics, including laser force cytology, with a goal to delivering adaptive manufacturing, full automation and standardized processes, products and patient outcomes. Chapter seven: Addressing manufacturing at scale for ATMP’s. Reducing costs through reducing batch failures and shrinking footprints, and targeting more focused critical quality attributes for potency but also patient efficacy. Reducing regulatory uncertainty in an uncertain environment to increase patient access to life saving cures. #cgt #bioprocess #oncology #CAR-T Thanks to BioPharm International and MJH Life Sciences®

Induced pluripotent stem cells (iPSCs) have revolutionized the way we explore human disease mechanisms and develop therapies. However, challenges like genetic instability, heterogeneity, and quality control remain a concern. At Syngene, we address these challenges by generating high-quality iPSCs followed by extensive characterization to ensure the quality of the final clones and their derivatives.   With our deep experience and expertise in this area, we provide comprehensive solutions to generate feeder-free and viral integration-free iPSC clones specifically designed for cellular assays and screening. Our end-to-end services include iPSC reprogramming, characterization, CRISPR and advanced nuclease-based gene editing, differentiation of iPSCs into multiple lineages, and in vitro assays using iPSC derivatives or primary cells.   Furthermore, our advanced CAR-T platform complements our iPSC capabilities, offering a comprehensive suite of services for cell and gene therapy research. Partner with Syngene to accelerate your drug discovery. For more information, visit the link in comments section 🔗   #iPSCs #DrugDiscovery #Syngene #discoveryservices

𝐀𝐭𝐬𝐞𝐧𝐚 𝐓𝐡𝐞𝐫𝐚𝐩𝐞𝐮𝐭𝐢𝐜𝐬 𝐏𝐮𝐛𝐥𝐢𝐬𝐡𝐞𝐬 𝐏𝐫𝐨𝐦𝐢𝐬𝐢𝐧𝐠 𝟏𝟐-𝐌𝐨𝐧𝐭𝐡 𝐃𝐚𝐭𝐚 𝐟𝐨𝐫 𝐆𝐞𝐧𝐞 𝐓𝐡𝐞𝐫𝐚𝐩𝐲 𝐢𝐧 𝐋𝐂𝐀𝟏 Atsena Therapeutics Atsena Therapeutics announced that 12-month safety and efficacy data from its Phase I/II trial of the investigational gene therapy ATSN-101 for Leber congenital amaurosis caused by biallelic mutations in GUCY2D (LCA1) were published in The Lancet. ATSN-101 is the first gene therapy under study for LCA1, a disease that causes severe vision impairment or blindness in infancy. In the trial, 15 patients received subretinal injections of ATSN-101. High-dose subjects showed a 100-fold improvement in dark-adapted full-field stimulus test (FST) and modest improvements in visual acuity after 12 months. All adverse events were mild or moderate, with most related to the surgical procedure and reversible with steroid treatment. “This is the first time LCA1 patients have been treated with gene therapy, making ATSN-101 a promising first-in-class treatment for this inherited retinal disease,” said Paul Yang, MD, PhD, lead author of the paper. “The improvements observed in retinal sensitivity as early as 28 days post-treatment are encouraging and highlight the durability of our investigational gene therapy.” The published manuscript is available online and will appear in The Lancet's print issue at a later date. #GeneTherapy #VisionRestoration #LCA1 #Ophthalmology #Biotech #ClinicalTrials #MedicalResearch

🔬 RNA delivery solution : a case study of base editing in Hutchinson-Gilford Progeria Syndrome (HGPS).   FlashRNA®, our cutting-edge RNA delivery technology, has shown remarkable efficiency in delivering an adenine base editor (ABE) and an sgRNA to target the LMNA gene mutation responsible for HGPS in mice. This precise correction reduces the production of progerin, the mutated protein responsible for accelerating aging in HGPS patients.   💡 Through our collaboration with Maria Eriksson's team at Karolinska Institute and the Institute for Basic Science, FlashRNA® is proven to be a powerful tool in genome editing to address complex, rare genetic disorders like progeria.   Key results: ✅ Efficient correction of LMNA gene mutation in treated cells, with more than 20% editing frequency ✅ Significant reduction in progerin expression and inflammation in skin cells. ✅ Long-lasting improvements in epidermal thickness and overall skin health, four weeks post-treatment.   With our state-of-the-art "plug & play" manufacturing and purification process, we ensure high-quality viral vectors from R&D through GMP-level production, supporting you at every stage of your development, from discovery to clinical trials.   👉 Get in touch with our experts : https://lnkd.in/e2SRW6Xg   #CDMO #mRNA #RNAtherapeutics #Geneticdisorders #Genomeediting #Baseediting

The power of predictive data insights for improved advanced therapy development and manufacturing. Thank you Chris Spivey for including LumaCyte and Sean Hart, PhD in this all star panel. Looking forward to sharing the full release when it goes live! Great snippet on the importance of real-time predictive analytics below…

🎉 Celebrating Rare Disease Day with New Lipids to Empower Gene Therapy Research At BroadPharm, to expedite drug delivery, we are constantly pushing boundaries to maximize the potential of ionizable lipids. Our latest R&D empowerment comes with TCL053 (pKa 6.8), a promising ionizable lipid used in the development of lipid nanoparticles (LNPs). TCL053 has demonstrated outstanding capabilities in delivering CRISPR-Cas9 mRNA, sgRNA, and Luciferase mRNA to various muscle tissues, exhibiting low immunogenicity and an enhanced safety profile. Additionally, TCL053 addresses a critical challenge in gene therapy – the non repeatable administration of Adeno-Associated Virus (AAV) vectors. With an encapsulation efficiency ranging from 95.8% to 98.5%, TCL053-LNPs present a compelling solution for rare diseases like Duchenne muscular dystrophy (DMD), necessitating repeated doses for treatment.  BroadPharm has synthesized a diverse range of TCL053 analogs, each meticulously crafted to optimize delivery efficiency. From multi-chargeable piperazine head replacements to tail modifications reducing from three to two hydrophobic tails, these analogs represent our commitment to advancing genetic therapies.  🔗 TCL053 & analogs —> https://lnkd.in/g5iCmwfT  #RareDisease #DMD #GeneTherapy #AAV #Research #RNA #mRNA #siRNA #LNP #DrugDelivery #Lipid #Ionizable #Cationic #Branched #Phospholipid #Cholesterol #PEGLipid #SM102 #ALC0315 #TCL053