Cell And Gene Therapy Innovations

The cell and gene therapy industry continues to evolve, what's shaping the future trajectory? There is a pivotal shift in biopharma and advanced therapies investment, with late-stage, clinically validated assets taking center stage. 🔬 Clinical Validation Over Platform Tech Investors are prioritizing Phase 2+ assets over early-stage platform technologies, favoring de-risked, late-stage therapies with clear regulatory pathways and commercial viability. This shift is crucial for CGT startups seeking funding—robust clinical data will be a necessity, not a luxury. 💰 VC and PE Consolidation in Healthcare The report forecasts a trend toward fewer, larger deals in life sciences, as investors double down on high-value, late-stage biotech plays. With CGT’s capital-intensive nature, securing investment will require strong clinical outcomes and strategic partnerships. 🌍 Global Specialization in Biopharma Regional dynamics will shape CGT investment: • North America leads in AI-driven drug discovery and cell-based therapies • Europe focuses on sustainable biomanufacturing and rare disease treatments • Asia dominates biosimilars and manufacturing scale-up 🤖 The AI & TechBio Convergence AI is rapidly transforming gene editing, cell therapy design, and biomanufacturing, streamlining regulatory approvals and accelerating pipeline development. Expect a growing synergy between biotech and techbio as automation and digital twins drive innovation. 🏆 Strategic Capital Allocation is Critical For CGT companies, success in 2025 will hinge on: ✅ Late-stage validation – Strong clinical assets will command the highest valuations ✅ Regulatory adaptability – Navigating FDA/EMA pathways efficiently ✅ Tech-enabled scale-up – Leveraging automation for efficient manufacturing The next wave of CGT breakthroughs will come from smart capital deployment, AI integration, and industry collaboration. The sector’s resilience is evident, but investors will demand clear paths to commercialization before committing capital.

"In a study published in Science, Triebwasser and co-first authors Laura Breda, PhD, and Tyler E. Papp demonstrated genome editing of HSCs in vivo (and ex vivo) through mRNA delivered by lipid nanoparticles (LNPs) decorated with targeting moieties. With the support of co-senior authors Stefano Rivella, PhD, from the Children’s Hospital of Philadelphia, and Hamideh Parhiz, PhD, from the Perelman School of Medicine at the University of Pennsylvania, they used LNPs targeting a stem cell factor on HSCs (CD117) for delivery of mRNA to correct human sickle cells ex vivo and to target HSCs in mice in vivo. For in vivo genome editing, the researchers delivered CD117-targeted LNPs with pro-apoptotic PUMA (p53 upregulated modulator of apoptosis) mRNA that affected HSC function in the bone marrow niche in vivo, which permitted nongenotoxic conditioning for HSCT. With cargoes like PUMA that can kill off targeted cells, Papp said that he sees this technology as eventually replacing the chemotherapy necessary to ablate malignant hemopathies that require HSCT. “Conventionally, CAR T-cell therapy is done through retroviral-based approaches that have a more permanent T-cell population, with patients showing continued success 10 years after they’ve been administered the T-cell,” said Papp. “One of the applications of this technology is for preconditioning for HSCTs or cancer chemotherapy. Instead of going through all of that, you just have to get one injection of these LNP-mRNA therapeutics, which, keep in mind, are acute—the mRNA expresses, degrades, and is gone from the body.” “The beauty of this mRNA-LNP approach is that it’s a highly modular platform where we are able to decorate the surface of these LNPs, which were the foundation for the most efficacious COVID-19 vaccines for Moderna and Pfizer, to target certain cell types, and we can modify the mRNA cargo to express (or not express) in certain cell types in the body,” said Papp, a research scientist in the lab of Drew Weissman, MD, PhD. “I think we’re on the verge of designing personalized therapeutics that can have a higher regulation of unintended side effects.”" Excerpts from Genetic Engineering & Biotechnology News article highlighting a targeted mRNA lipid nanoparticle (LNP) technology for in-vivo genome editing and protein replacement therapy, developed by Hamideh Parhiz, Stefano Rivella, and Tyler Ellis Papp- congrats! Link to Science publication below: In vivo hematopoietic stem cell modification by mRNA delivery https://lnkd.in/eRy8buWA https://lnkd.in/e8sFWgeU

Gene therapy restores hearing, even in a 24-year-old who was born deaf (which is a big deal, not just for them but also the science): 🧬A single shot of gene therapy restored hearing in 10 patients aged 1 to 24 with congenital deafness caused by OTOF gene mutations 🧬 While this is not the first Gene therapy for deafness, the surprise was the 14- and 24-year-old participants saw dramatic improvements, something researchers didn’t expect based on previous studies 🧬 Average hearing improved from 106 decibels (profound deafness) to 52 (functional range) within six months 🧬 Hearing gains were often rapid, with most patients showing improvement within the first month 🧬 One 7-year-old recovered enough to hold daily conversations and hear rain for the first time, despite having a cochlear implant in the other ear 🧬 The therapy uses an adeno-associated virus to deliver a working copy of the OTOF gene through a single injection to the inner ear #digitalhealth

Can AI crack the longevity code? OpenAI's venture into biological data is turning heads in the science community. Their latest project revolves around engineering proteins, specifically designed to enhance the efficiency of turning regular cells into stem cells. This marks a significant shift for OpenAI as it's their first time diving into biological discovery. Using their model, GPT-4b micro, they've managed to outperform human efforts in re-engineering Yamanaka factors—proteins crucial in cell reprogramming. This innovative step comes with backing from Retro Biosciences, a company aiming to lengthen human lifespan. By manipulating Yamanaka factors, OpenAI's model suggests ways to improve how these proteins work, making the transition of skin cells to stem cells markedly more efficient. Preliminary results show that modifications suggested by the AI have increased the effectiveness by over 50%. This could potentially lead to breakthroughs in rejuvenating animals, creating human organs, or generating replacement cells. In related areas, developments such as digital twins of human organs could redefine medical treatments. On the other hand, unproven therapies like exosomes serve as a cautionary tale, reminding us of the need for scientific backing. As for Neuralink, expect more trials but patience is key for product realization. With these patterns, it's evident the intersection of AI and biology is just beginning to unravel its full potential. https://lnkd.in/gTzJZa3G #ai #openai #longevity #science #biology

Revolutionizing #Longevity: AI’s Game-Changing Role in Regenerative Medicine #OpenAI and Retro Biosciences are pioneering a transformative shift in healthcare. At the heart of this revolution is GPT-4b Micro—a specialized AI model tailored to advance stem cell research and redefine regenerative medicine. What makes GPT-4b Micro extraordinary? By optimizing Yamanaka factors—the proteins critical to cellular reprogramming—it has achieved a 50x increase in efficiency for converting adult cells into induced pluripotent stem cells (iPSCs). This precision accelerates breakthroughs in: • Stem cell production for scalable medical applications • Tissue engineering, paving the way for bioengineered organs • Cell-based therapies for conditions like Alzheimer’s, diabetes, and heart disease GPT-4b Micro combines deep learning with molecular biology to analyze vast datasets, predict protein interactions, and model complex biological processes. Its ability to simulate experiments reduces reliance on trial-and-error in labs, drastically cutting the time and cost of research. Here’s why this matters: 🔹 Organ shortages: This model could lead to lab-grown organs, addressing the global transplant crisis. 🔹 Aging research: By unlocking cellular rejuvenation, it lays the foundation for reversing age-related decline. 🔹 Personalized medicine: GPT-4b Micro offers the potential to tailor treatments for individual patients based on their unique cellular profiles. Backed by Sam Altman’s $180M investment in Retro Biosciences, GPT-4b Micro demonstrates how AI and biotechnology are converging to create solutions once thought impossible. This partnership could mark the beginning of a new chapter in human longevity, extending healthspan and quality of life for millions. While still in its early stages, GPT-4b Micro offers a glimpse into the transformative potential of AI in biology. Imagine a future where regenerative medicine is faster, more accessible, and profoundly impactful. 💡 What do you think about AI’s role in advancing longevity science? Let’s dive into the discussion below! #AI #LongevityScience #RegenerativeMedicine #HealthcareInnovation #DrGPT

“The first thing just worked,” Boris Power, head of OpenAI’s applied research team, told me ahead of the company's latest announcement. “That’s rarely the case in research. We were skeptical for a very long time.” Power was talking about GPT-4b micro, a protein-focused variant of its GPT-4o model that it built in collaboration with Retro Biosciences. The research shows how LLMs could be applied to life sciences research. In this case, by making variants on the famed Yamanaka factors that were more efficient in turning mature cells back into stem cells. Retro CEO "Joe Betts-LaCroix" expects to use some of these AI-made proteins in a preclinical research program, seeking to reprogram patient's cells. “Because reprogramming is in the loop, the timing and efficiency of it matter for the patient in terms of how many starting cells do you need, how long does the patient have to wait around,” Betts-LaCroix said. “It can work with canonical Yamanaka factors, but as we’re optimizing, we’re like, ‘Why?’ They’re worse.” My latest exclusive on the AI bio frontier at Endpoints News: https://lnkd.in/gU8_8ppf

Imagine gene therapy treatments costing $100,000 instead of $2 million per dose. A new review shows this isn't just wishful thinking – continuous bioprocessing could reduce manufacturing costs by up to 80%, potentially transforming patient access to these life-changing treatments. A exciting review paper by Lorek et al. reveals how the shift from traditional batch processing to continuous manufacturing may revolutionize gene therapy production. The innovation lies in running multiple production steps simultaneously with constant material flow, enabled by multi-column chromatography systems and advanced process analytic technology (PAT). What makes this particularly exciting is how continuous processing addresses the core challenges of gene therapy manufacturing. Traditional batch processing requires larger facilities, faces significant downtime between batches, and struggles with consistency. In contrast, continuous processing achieves higher productivity at a smaller scale while improving product quality – critical factors for reducing those astronomical million-dollar-plus treatment costs. The technology behind this transformation is fascinating. Multi-column chromatography systems now enable continuous capture and purification of viral vectors, improving productivity nearly threefold while maintaining yields above 82%. Even more impressive is the integration of real-time monitoring through process analytical technologies. These systems use in -line spectroscopic sensors, dynamic light scattering, and rapid analytics to track critical quality attributes in real-time, ensuring consistent product quality while dramatically reducing manufacturing time and costs. The implications for patient care are profound. By reducing facility footprint, increasing productivity, and improving product quality, continuous processing could help transform gene therapies from last-resort options into more widely accessible treatments. Early studies suggest manufacturing costs could drop by 60-80% compared to traditional batch processing – a game-changing reduction that could dramatically expand patient access. What excites me most is how these advances are converging with artificial intelligence and automation. Real-time monitoring systems coupled with advanced process controls are enabling unprecedented precision in manufacturing, ensuring every batch meets the highest quality standards while maximizing efficiency. We're witnessing a fundamental shift in how gene therapies are manufactured. The question isn't just about cost reduction – it's about reimagining production to make these transformative treatments accessible to everyone who needs them. What are your thoughts on these developments? How do you see these manufacturing innovations reshaping the future of genetic medicine? #GeneTherapy #Biotechnology #ContinuousProcessing #Healthcare #Innovation #PatientAccess

FDA approves two gene-modified autologous cell therapies for sickle cell disease, including first that uses CRISPR – paving the way for expanded use of personalized gene-engineered cell therapies. Bespoke autologous cell therapies have a niche as living therapeutics in clinical use cases where immune function and compatibility are paramount for potency. Enter the FDA approval of bluebird bio’ Lyfgenia as well as Vertex Pharmaceuticals’ Casgevy, both for SCD. Although the FDA approval of a gene engineered autologous cell pharmaceutical was first achieved with Novartis’ Kymirah in 2017, the FDA’ approval of Vertex’ Casgevy speaks to its assent of CRISPR-mediated gene editing as meeting safety equipoise. This also paves the way for FDA-sanctioned commercial manufacturing schemes for use of CRISPR gene-engineering technology – in addition to lentiviral transduction – as commercially viable means of manufacturing bespoke personalized gene-engineered cell therapies for use in other catastrophic illnesses with unmet medical needs. Disruptive gene-engineering technologies coupled with open market competition will be drivers of sustainable and accessible living therapeutics treatments and cures now and in future. Congratulations to the legion early innovative scientific discoverers and the risk-taking moxxi of CGT commercial developers to bring these living  pharmaceutical platforms over the marketing approval goal line.

In December of 2023, the FDA approved two gene therapies to treat sickle cell disease, a genetic blood disorder that affects about 100,000 Americans. What was exciting about these two therapies? Well, many things. But two big ones are: 1. They are the first two gene therapies to treat, and potentially cure, sickle cell disease. Before these two therapies, the only other transformative option available was to use bone marrow transplants which come with a myriad of other challenges, such as donor matching. But now, with these two therapies, patients can effectively "be their own match." 2. One of the therapies - named Casgevy and made by Vertex Pharmaceuticals and CRISPR Therapeutics - is the first FDA approved medication developed with #CRISPR technology. A huge milestone. Next gen cell & gene therapies are challenging assumptions ("yes, we could cure that!") and changing lives. Now, there's still challenges to overcome, such as increasing access to these life-changing therapies, but we're moving in the right direction. If you're interested in learning more about cell & gene therapies (CGTs), or interested in a primer on what CGTs even are, check out my latest #TECHTalks podcast with Hussain Mooraj, Deloitte's Next Gen Therapy Leader. Jam packed with info, my guess is you'll walk away learning something new. And if not, let me know, and your next coffee's on me! Here's to the future, Raquel Marie Gaudaire, E. Janelle Hughes, Nina Rebolleda Martinez, Roshni Sharma Many thanks as always to this incredible team!

The quiet undercurrent at ASGCT this year? Gene therapy doesn't need more hype.  It needs validation: Because despite the recent doom and gloom around cost, safety, and trial setbacks… We’re already seeing the science respond to those criticisms. 1. Full genome characterization is here. Posters from AskBio, Gordian, and Capsida showed long-read ONT sequencing workflows that map exactly what’s inside an AAV capsid. That’s a game changer for potency, safety, and consistency. 2. We’re finally unlocking epigenetic control. More groups are tracing how capsid sequence, genome localization, and chromatin state shape transgene expression. These are the insights that can reduce dose—and expand access. 3. AI-designed capsids are getting clinical-ready. Eric Kelsic's talk at Dyno showed best-in-class AAV vectors tuned for potency in CNS, eye, and muscle - with significantly improved liver detargeting and scaled optimization. 4. Manufacturing is catching up. Shameless plug here, but we’re building the systems needed to bring these next-gen vectors into the clinic safely, affordably, and at scale.  (As in, a ~10x reduction in upstream manufacturing costs) Because none of this matters if we can't make it work economically. 5. Payload design is getting smarter. Capsids are one thing.  But teams like Jude Samulski's are tackling the payload, optimizing regulatory elements, minimizing silencing, and building in durability.  And in doing so, they have dramatically increased potency (and reduced dose sizes). We can’t afford to separate capsid and genome innovation anymore.  They have to co-evolve. 6. Validation is still the bottleneck. We’re seeing brilliant work from labs, biotech and startups.  But unless we push hard for clinical validation - with the right CMC, analytics, and trial designs - we’ll stay stuck in preclinical limbo. But here’s the main takeaway for me: 𝗪𝗲 𝗻𝗲𝗲𝗱 𝗺𝗼𝗿𝗲 𝗵𝗮𝘀𝘁𝗲, 𝗹𝗲𝘀𝘀 𝘀𝗽𝗲𝗲𝗱. If we rush these breakthroughs into the clinic without urgent, rigorous validation, we risk setbacks that have nothing to do with the tech - and everything to do with execution. Let’s not blow the opportunity. We have the tools.  Now we need to translate them - carefully, collaboratively, and with the clinic in mind. What caught your attention at ASGCT this year?