Recent Breakthroughs in Research and Development

A #Breakthrough Year for T Cells This year has been transformative for T cell therapies in the fight against cancer, as reviewed by Rigel Kishton and me in today’s issue of Nature Cancer (https://rdcu.be/d3R8D). With three FDA approvals, 2024 has underscored the clinical power of #Tcells -- living #immunotherapies capable of achieving results where all other treatments fail. Key Approvals of 2024 -> #Lifileucel (Amtagvi): The first #TIL-based therapy for unresectable/metastatic melanoma, approved in February. -> Afamitresgene (Tecelra): The first #TCR-engineered therapy for solid tumors, approved in August for synovial sarcoma. -> Obecabtagene (Aucatzyl): The 7th #CAR T therapy for B cell hematologic malignancies, approved last month. 🚀 These therapies are clinically remarkable. Engineered from a patient’s own T cells, they deliver life-changing responses for patients with no other options. I’ve had the privilege of contributing to these advancements and witnessing their profound impact. The Promise of TIL Therapies TIL-based therapies hold transformative potential. By recognizing tumor #neoantigens -- expressed #mutations, cancer germline antigens, and even “#darkgenome” products like #HERVs or #pseudogenes -- T cells can achieve durable, complete responses. CD4+ and CD8+ T cells bring the ability to directly or indirectly eliminate tumors where traditional therapies fall short. Despite these advances, the oncology capital markets remain skeptical. Cell therapy companies face immense challenges: -> Development Costs: Complex manufacturing, high trial expenses, and stringent regulations. -> Safety Concerns: Risks like cytokine release syndrome and lymphodepletion-associated toxicities. -> Commercialization Hurdles: High prices, uncertain reimbursement, and cumbersome logistics. The result? T cell-based immunotherapies can land with a thud from investors concerned about small target markets and costly treatment delivery. ⚡ Technology as a Solution The future of T cell-based therapies looks brighter with technological innovation: -> #AI/ML for Transcriptomics and Genomics: Personalizing T cell products for individual patients. -> Cheaper #Sequencing: Accelerating tumor neoantigen target discovery. -> Improved Culture Methods: Enhancing T cell #stem cell qualities for durable efficacy. While #Tcellengagers and #bispecificantibodies gain investor interest for their transient solid tumor activity, these treatments are rarely curative. TIL therapies, on the other hand, stand on the cusp of delivering transformative, long-term responses in patients with common solid tumors. The journey isn’t easy—financial skepticism, logistical hurdles, and scientific complexity remain—but the horizon for T cell therapies is filled with extraordinary possibility. Here’s to the progress we've made and the breakthroughs that lie ahead. 🎇 #immunotherapy #celltherapy #carT #TIL #oncology

Quite a nice (and updated) review -RNA therapeutics and LNPs for extrahepatic delivery LNPs have become a cornerstone in delivering RNA therapeutics, successfully used in mRNA vaccines and gene therapies. Despite their success, LNPs' tendency to preferentially accumulate in the liver remains a critical limitation. This liver tropism hinders their effectiveness in treating diseases in other organs, such as the lungs, brain, and pancreas. 🔬 Recent research has made significant strides in re-engineering LNPs to deliver RNA to organs beyond the liver. One approach is to adjust the composition of LNP formulations, either by adding a cationic lipid (like DOTAP) or replacing the ionizable lipid's ester linkers with amide linkers. These modifications change the physicochemical properties of LNPs, influencing the biomolecular corona that forms post-administration, which ultimately determines organ-specific targeting. For instance, lung-targeted LNPs can transfect up to 65% of endothelial cells and 40% of epithelial cells in the lungs, demonstrating a potential breakthrough for treating pulmonary diseases like cystic fibrosis and pulmonary fibrosis. Spleen-specific delivery has been achieved by incorporating anionic lipids, enabling the targeting of immune cells like macrophages and T cells, essential for in vivo immunotherapy applications. Meanwhile, LNPs designed for bone marrow delivery are showing promise in treating hematopoietic disorders like sickle cell disease. 🧠 Still, delivering RNA to the brain remains a considerable challenge (you know, the usual BBB). However, promising strategies, like adding neurotransmitter-derived lipids to LNP formulations, are showing early success in crossing this barrier, paving the way for treating neurological diseases. 🎯 As we look to the future, designing LNPs that can target specific cell types and improve safety profiles is paramount. Advances in overcoming physiological barriers, such as the BBB and tissue-specific targeting, will revolutionize how we approach gene therapies for previously untreatable conditions. From organ-selective LNPs to fine-tuned biomolecular coronas, the future of RNA delivery is more promising than ever. Learn more here: https://lnkd.in/ecQjkNaq #Nanomedicine #LipidNanoparticles #GeneTherapy #RNA #BiotechInnovation #TargetedDelivery #DrugDelivery

Last month, a team of scientists and physicians achieved something extraordinary: they developed and delivered the first-ever personalized #CRISPR therapy to treat an infant with a life-threatening #raredisease — in just six months. A one-letter change in the baby’s DNA was corrected using a custom-built gene editor. The child, who was once facing the prospect of a liver transplant, is now steadily improving. It’s a powerful example of what’s becoming possible at the intersection of #science and #technology, urgency and purposeful ambition. And this isn’t an isolated win. Across labs, clinics, and companies, CRISPR is being used as a therapeutic modality to correct inherited disorders, engineer immune cells, disable viral DNA, and even edit entire chromosomes. New gene-editing systems—like TIGR-Tas, unveiled earlier this year—are expanding what’s possible in tissues or conditions where current tools fall short. Clinical results are emerging fast—and the pace of #innovation is only picking up. At Recursion, we’re also applying #geneediting tools like CRISPR beyond therapeutics—using the technology as a tool to better understand #biology at scale. By systematically “knocking out” thousands of individual genes and measuring how those changes affect cell behavior, we’re generating large, structured datasets that feed directly into #AI models. This is helping us uncover new biological relationships and power #drugdiscovery in ways that were previously unimaginable. What ties all of this together is a commitment to applying game-changing #innovation in service of real, urgent human needs. It signals a much-needed mindset shift in #healthcare and #biopharma: to move faster, think bigger, and tackle challenges once considered out of reach—and to truly deliver on the promise of #precisionmedicine. And we’re seeing this ambition in many other areas as well – just last week, for example, GRAIL announced more promising than ever performance stats for its #Galleri blood test for the early detection of 50+ types of #cancer. There’s still work ahead to ensure breakthroughs translate into broad, equitable impact. But this moment – this momentum – is worth pausing to recognize. We’re no longer just imagining a future where science works smarter and faster for patients. We’re building it.

Groundbreaking Advancements in Gene Editing Technologies: A Paradigm Shift in Precision Medicine Recent developments in gene editing technologies have ushered in a new era of precision medicine, offering unprecedented opportunities for therapeutic interventions and scientific research. Here's an overview of the latest advancements: 1. Enhanced CRISPR Systems: Novel synthetic RNA-guided nucleases demonstrate superior specificity to conventional Cas9 proteins, significantly reducing off-target effects. 2. Base Editing: This technique enables precise chemical alterations of DNA bases without inducing double-strand breaks, enhancing accuracy and minimizing unintended modifications. 3. Prime Editing: An advanced form of gene editing capable of generating or correcting any point mutation, surpassing the limitations of base editors. This technology shows particular promise for addressing mutations associated with genetic disorders such as sickle cell anemia. 4. CRISPR-mediated Multiplexed Genome Engineering: This approach facilitates simultaneous analysis of multiple genetic mutations, enhancing the efficiency and complexity of gene function studies. 5. Engineered Base Editors: Recent developments include C:G to G:C base editors (CGBEs) and A:T to C:G base editors (ACBEs), expanding the repertoire of possible genetic modifications. 6. Optimized Prime Editing: Researchers have enhanced prime editing efficiency through the engineering of prime editors (PEs) and optimization of pegRNAs, improving expression, nuclear localization, and degradation resistance. 7. CHIME and X-CHIME Systems: These novel approaches enable more precise and versatile gene editing in immune cells, allowing for combinatorial, inducible, lineage-specific, and sequential genetic modifications. 8. In vivo CRISPR Delivery: Researchers have successfully performed gene editing in murine lung cells using enhanced lipid nanoparticles to deliver CRISPR-Cas9 systems, opening new avenues for treating pulmonary conditions such as cystic fibrosis. 9. CRISPR-mediated Elimination of Antimicrobial Resistance Genes: This application of CRISPR technology addresses antibiotic resistance by removing antimicrobial resistance genes from bacteria. These advancements are a significant leap forward in our ability to manipulate genetic material with unprecedented precision. As scientists continue to refine these technologies, we can anticipate transformative impacts on personalized medicine, functional genomics, and the treatment of genetic disorders. #GeneEditing #Biotechnology #CRISPR #PrecisionMedicine 

𝐀𝐈 𝐢𝐬 𝐜𝐨𝐥𝐥𝐚𝐩𝐬𝐢𝐧𝐠 𝐭𝐢𝐦𝐞𝐥𝐢𝐧𝐞𝐬 𝐢𝐧 𝐦𝐞𝐝𝐢𝐜𝐢𝐧𝐞, 𝐚𝐧𝐝 𝐫𝐞𝐰𝐫𝐢𝐭𝐢𝐧𝐠 𝐭𝐡𝐞 𝐞𝐜𝐨𝐧𝐨𝐦𝐢𝐜𝐬 𝐨𝐟 𝐜𝐮𝐫𝐞𝐬 A few years ago, predicting a protein’s structure took months or even years. Then came AlphaFold, DeepMind’s Nobel-winning breakthrough, unlocking the ability to understand proteins and disease mechanisms at scale and speed. This led to Alphabet’s spin-off, 𝐈𝐬𝐨𝐦𝐨𝐫𝐩𝐡𝐢𝐜 𝐋𝐚𝐛𝐬, now using AI to design therapies with $600M in funding and its first human trials underway for cancer and immune disorders. ▫️ The speed of progress: Every six months, AI advances like a full human year. What once took decades now unfolds in quarters. ▫️ The cost collapse: AI is driving the cost of drug discovery and testing so low that researchers can now explore thousands of drug candidates and disease targets at once, including treatments that would have been dismissed as too niche or unprofitable just a few years ago. ▫️ The scale of exploration: AI has already helped identify or repurpose over 3,000 drugs currently in clinical trials. We’re already seeing the results. Northwestern researchers, for example, used AI-enhanced screening to repurpose 𝐩𝐢𝐩𝐞𝐫𝐚𝐜𝐢𝐥𝐥𝐢𝐧, a decades-old FDA-approved antibiotic, for Lyme disease. In mouse studies, it cured infection at one-hundredth the dose of standard treatment without harming gut microbiota. That breakthrough emerged in days, not years, at a fraction of traditional costs. 🔺 𝐖𝐞 𝐚𝐫𝐞 𝐰𝐢𝐭𝐧𝐞𝐬𝐬𝐢𝐧𝐠 𝐚 𝐟𝐮𝐧𝐝𝐚𝐦𝐞𝐧𝐭𝐚𝐥 𝐬𝐡𝐢𝐟𝐭. AI isn’t just speeding up medicine, it’s enabling exploration and validation at scales and price points previously unthinkable. And every six months, the landscape tilts even further. This is what leaders need to see: the weight of the opportunity, and the urgency to align their thinking to the pace of this change. #AI #Healthcare #DrugDiscovery #GenAI #FutureOfWork #mindsetchange Forbes Technology Council Gartner Peer Experiences InsightJam.com PEX Network Theia Institute VOCAL Council IgniteGTM IA FORUM 𝗡𝗼𝘁𝗶𝗰𝗲: The views within any of my posts, or newsletters are not those of my employer or the employers of any contributing experts. 𝗟𝗶𝗸𝗲 👍 this? feel free to reshare, repost, and join the conversation!

"Australian scientists have successfully developed a research system that uses 'biological artificial intelligence' to design and evolve molecules with new or improved functions directly in mammal cells. The researchers said this system provides a powerful new tool that will help scientists develop more specific and effective research tools or gene therapies. Named PROTEUS (PROTein Evolution Using Selection) the system harnesses 'directed evolution', a lab technique that mimics the natural power of evolution. However, rather than taking years or decades, this method accelerates cycles of evolution and natural selection, allowing them to create molecules with new functions in weeks. This could have a direct impact on finding new, more effective medicines. For example, this system can be applied to improve gene editing technology like CRISPR to improve its effectiveness." #bioai

The most exciting life science isn’t coming from a single category anymore - it’s coming from the places in between. Our current Innosphere cohort reflects this shift. The companies we’re supporting are blending disciplines, disrupting boundaries, and reshaping what healthcare innovation looks like. Here’s a snapshot of the cohort’s composition: 🩻 30% medical devices 💊 20% biopharma and biotech 🧠 25% digital and health technologies The remainder are a powerful mix of advanced materials, diagnostics, and breakthrough platforms. And some examples of their innovative solutions? 🧬 A drug-device combination pairing pharmacology with engineered sound stimulation of the brain for age-related central hearing loss, a condition preventing 800M patients from hearing in noisy environments. 🧪 An injectable regenerative biomaterial designed to stimulate brain repair and neurological recovery after stroke, with the potential to extend the treatment window months beyond what it is today. 📄 A digital tool that uses large language models to pre-write high-quality radiology reports, reducing reporting time by 30% and improving consistency. 🧫 A regenerative medicine company that’s creating custom 3D-bioprinted breast tissue using a patient’s own fat cells. 🔥 A revolutionary single-use flexible robot endoscope offering unparalleled precision, stability, and control, reducing technical complexity and procedure times. These products are signals that the most impactful innovation is coming from the convergence of disciplines: AI with diagnostics, advanced materials with biologics, and digital tools with therapeutic interventions. As investors, as industry leaders, and as builders of what comes next, we should be paying attention. These startups are creating entirely new possibilities for how we diagnose, treat, and care for patients. My team is proud to support this generation of founders, and I believe the companies in this cohort aren’t just future-ready - they’re future-defining.

Another wild week in biotechnology: 1. Now you can track cellular gene expression patterns, using ultrasound, from outside the body. (The technology is built on gas vesicles, which I’ve written about before.) If you had said this would be a thing 10 years ago, nobody would have believed you. Mikhail Shapiro 2. Researchers made "an autobioluminescent transgenic mouse line," using bacterial DNA, that constantly emits photons. (Image below.) 3. Whole-genome sequencing of microbes floating in the air is becoming more popular. (Fun fact: Microbes travel all the way from the Sahara Desert to New York by riding motes of sand into the atmosphere.) 4. There's a new toolkit to program multicellular behaviors in Baker’s yeasts. Tom Ellis 5. Rational design of tunable, fluorescent DNA aptamers. The researchers used them to build “responsive nanostructures that light up upon activation.” 6. Scientists made sixteen new cytosine base editors, which outperform existing base editors 81.5 percent of the time. 7. A new competition is offering $30,000 in cash prizes for teams that can design the best PETase enzymes. The Align Foundation / Erika Alden DeBenedictis 8. Lab-grown sperm and eggs are likely a few years away. I’d wager this will happen within 3 years. 9. Cryo-EM structures of the measles virus polymerase mark an important step toward new therapeutics. 10. Chai-2 is “a multimodal generative model that achieves a 16% hit rate in fully de novo antibody design.” 11. A new method can eliminate multiple chrosomes inside of yeast cells, thus making them haploid. 12. A multi-adjuvant neoantigen vaccine for melanoma. 13. A single-cell multi-omics atlas of rice. Super important, considering rice is the main source of food for more than half of people on Earth. 14. SciArena ranks 23 LLMs based on their accuracy answering science questions. 15. Organoids grown in the lab now have vessels to transport blood and nutrients. 16. Researchers tracked how 214 diseases spread across Europe and Asia over the past 37,000 years by sequencing 1,313 ancient humans. 17. BioEmu is a deep learning model for emulating protein equilibrium ensembles that also incorporates “over 200 milliseconds of molecular dynamics (MD) simulations, static structures and experimental protein stabilities.” 18. A new model for IVF was “trained on…18 million time-lapse embryo images.” 19. First malaria treatment approved for infants weighing less than 4.5 kilograms.