Podovirus

What if you could build biology in a tube, no cells required? Invitris is a Munich-based cell-free synthesis company starting with bacteriophages. Kilian Vogele, co-founder of Invitris, joins Jessica and Joe to explain how cell-free phage production works — and why they're building toward a "phage printer" that could sit in a hospital.Topics covered:• How cell-free phage production actually works• Why removing bacteria removes a lot of contamination problems• Phages as Lego sets — mix-and-match engineering• Building a phage printer for hospitals• Where AI-generated phages fit (and don't)• What it takes to get cell-free phages into a clinical trialKilian Vogele is the co-founder of Invitris, a Munich-based cell-free synthesis company currently focused on bacteriophage production. Trained as a physicist at TU Munich, he co-founded Invitris out of a 2018 iGEM project and has been building toward decentralized, on-demand cell-free manufacturing — starting with phages.

Chip Schooley (UC San Diego, IPATH) and Graham Hatfull (University of Pittsburgh) join us to discuss why phage therapy needs biologists and clinicians collaborating — and what the HIV field’s playbook can teach us.Topics covered:• Why they organized an academic phage conference in Washington, D.C.• The state of in vitro phage assays and the reproducibility problem• How to design phage clinical trials that actually teach us something• Phage resistance, fitness trade-offs, and the role of the immune system• What HIV’s journey from 1988 to 1998 tells us about where phage therapy is headed• Why synthetic biology is the future of phage therapeutics• The need for young scientists entering the fieldGuests:Chip Schooley — Co-founder, IPATH Phage Therapy Center, UC San Diego. Physician behind the Tom Patterson case. HIV research veteran.Graham Hatfull — University of Pittsburgh. Runs the world’s largest phage collection. Creator of SEA-PHAGES.Hosts:Jessica Sacher & Joe CampbellLinks:IAS-USA: The conference Chip & Graham describe in the episode was sponsored by the International Antiviral Society-USA (Executive Director: Donna Jacobsen): https://www.iasusa.org/

Can AI design living organisms from scratch? Samuel King and Claudia Driscoll from the Arc Institute used genome language models to generate functional phages—and 16 of them actually worked in the lab. Not only that, they killed bacteria equally or better than the natural phage the team used as a template. In this episode, we dig into how they did it, what it means for phage research, and why this could be a new way to explore evolution and design genomes.What we covered:• How genome language models work (ChatGPT, but for DNA)• Training on millions of phage genomes with Evo-1 and Evo-2 • The creativity (from biologists!) required to figure out how best to filter generated sequences• Going from 4000 selected sequences in silico, to 300+ synthesized candidates, to 16 working phages• Fresh phage lab protocols for new ways to look at phage fitness• Phage "personalities" that emerged from the generated candidates• Watching recombination occur among a cocktail of designed phages• Cost realities: hundreds of dollars per 5kb genome candidate, but emerging ways to reduce it exist!• Good news: All tools are open source and free to use!The preprint:Samuel H. King, Claudia L. Driscoll, David B. Li, Daniel Guo, Aditi T. Merchant, Garyk Brixi, Max E. Wilkinson, Brian L. Hie (2025-09-17). Generative design of novel bacteriophages with genome language models | bioRxiv. biorxiv.org. Retrieved November 8, 2025, from https://www.biorxiv.org/content/10.1101/2025.09.12.675911v1More resources:• Arc Institute Evo browser interface: https://arcinstitute.org/tools/evo• GitHub (open source code): Evo2: https://github.com/ArcInstitute/evo2) • Hugging Face (model downloads): https://huggingface.co/arcinstituteGuests:Samuel King: PhD candidate, Stanford/Arc Institute, Brian Hie's lab; follow @samuelhking on XClaudia Driscoll: Postdoc, Arc Institute, Brian Hie's lab, follow @driscoll_cl on XAlso follow @BrianHie, @arcinstitute, @stanford on X for more from this team!

"It's unacceptable to just tell this poor patient, there's nothing I can do to help you... That's when I thought, okay, well, what about kind of pushing the boundaries a bit here and thinking about phage therapy?" - Dr. Marisa AzadJoin us for an inspiring conversation with Dr. Marisa Azad, a clinician-scientist at The Ottawa Hospital who is pioneering the treatment of chronic infections using phage therapy. Dr. Azad shares her journey from microbiology PhD to orthopedic infectious disease specialist, and how a desperate patient case led her to become the first in Canada to use phage therapy for prosthetic joint infections.Here's a taste of what we covered:1. 🦠 The challenges of treating orthopedic infections, and how the problem is typically being dealt with in Canada (hint: MULTIPLE repeated surgeries for years is normal)2. 🧪 How Dr. Azad navigated regulatory hurdles to bring phage therapy to Canada, and what it was like working with Health Canada (Canada's FDA) to get approval3. 💉 Insights on phage administration and patient immune responses: what she's learned and what barriers she sees4. 🔬 The importance of collaboration in advancing phage therapy research, and what's left for researchers to figure out5. 👩‍🔬 How crucial it is to support women in science and medicine, still in 2025, especially in innovative fields that require taking steps your field isn't taking (which require extra bravery and support systems!)6. 🏥 Bridging the gap between basic science and clinical practice: how Dr. Azad weaves together both ways of thinking, all with patient benefit as her central driverYou can also watch the episode on YouTube: https://youtu.be/5TKhgFplvfUWant to learn more?- CBC (Canada's national news outlet)'s coverage of Dr. Azad's successful case, and how patient Thea Turcotte recovered- Dr. Azad's recent publication on phage therapy for PJI (an n-of-1 clinical trial)- Our recent Podovirus interview with Cytophage CEO Steven Theriault, whose Winnipeg-based company prepared the phages for Dr. Azad's patient, and who is partnering with her as the phage manufacturer for future cases- Since Dr. Azad's success last year, Health Canada is beginning to enable more phage therapy: a PJI phage treatment has just taken place in Calgary by a separate group — watch the news segment here

"This feels just like the early days of the HIV crisis. People are dying, you're not hearing about it. We need a group like ACT UP to bring this to the public. We're not going to get phage therapy until people start demanding we have it." On this episode, we talk to phage therapy patient advocate Chris Shaffer about how he fought for access to phage therapy to save his own life, and how it's led him to advocate on behalf of other patients being told there's "nothing left" for their infections. He draws parallels between phage advocacy and 1980s AIDS activism, while sharing his successful treatment journey to Tbilisi, Georgia for phage therapy. He shares his vision for a patient-centered future where anyone, not just the well-connected or the lucky, can access phage therapy if it could help them. Here's a taste of what we covered:1. 🦠 Chris's battle with a drug-resistant infection that antibiotics couldn't cure, and how after two years of suffering, he was completely cured in just four months with phage therapy2. 🧪 The major obstacles to phage therapy access in the US: lack of awareness among doctors, patient trust issues, and difficulty finding phages that match specific infections3. 🏥 The striking cost difference: Chris's complete phage treatment at Eliava (including doctor visits, tests, and therapy) cost $4,600 vs. $10,000+ for just a single round of IV antibiotics in the US4. 🔬 How the FDA actually considers phages safe enough that they don't require the same safety testing as antibiotics - but this information isn't reaching patients or doctors5. 📢 Why Chris believes we need more vocal advocacy similar to the HIV/AIDS movement in the 1980s-90s to push for greater phage therapy access6. 📱 Practical ideas for improving access through non-profit phage centers, better education for medical students, and targeted communication strategiesLearn more:- Chris Shaffer's book about his phage therapy journey: https://www.amazon.com/FINDING-PHAGE-Partnered-Bacterial-Superinfection/dp/1733418296- Chris’ website: https://phagetherapyusa.com/- Case study on Chris’ case, published in the International Journal of Clinical Virology: https://www.clinvirologyjournal.com/articles/ijcv-aid1059.php- Eliava Phage Therapy Center in Tbilisi, Georgia: https://eliavaphagetherapy.com/ - 2021 FDA-NIAID Workshop on Phage Therapy transcripts mentioned during the conversation: https://www.fda.gov/media/159401/download- Pranav Johri's case study that helped Chris trust phage therapy: https://pubmed.ncbi.nlm.nih.gov/37790805/- An youtube interview we did with Pranav about his story: https://www.youtube.com/watch?v=V-Qso4q52CY- An interview we published in Capsid & Tail on Pranav's story: https://phage.directory/capsid/phage-therapy-access-india#article- The PASTEUR Act, which Chris mentions: a bill in US congress (still has not passed) on changing how antimicrobials can be paid for by the government: https://www.contagionlive.com/view/an-update-on-the-pasteur-act

"I was so biased. I knew too much and that's why we couldn't see the obvious answer that was right in front of us for years."In this episode of the Podovirus Podcast, we explore the intersection of AI and phage biology with Professors José Penadés and Tiago Costa from Imperial College London. They share their recent discovery about phage-inducible chromosomal islands (PICIs) and how Google's new (not-yet-released) AI co-scientist tool independently reached the same conclusions they had spent years working toward—revealing how tailless phage capsids can bind with different phage tails to expand their host range.Here's a taste of what we discussed:1. 🧬 First, the biology: José and Tiago discovered that sometimes the end product of a viral lifecycle isn't infectious (yet). It might instead float around as a half-virus (a 'tail-less capsid'), and even mix and match with halves (tails) of other viruses floating around, enabling it to get into a vast array of totally different cells with one simple genetic code. This is the story of PICIs (phage-inducible chromosomal islands). 2. 🤖 How Google's AI co-scientist tool—without access to their unpublished data on this project—accurately proposed the hypotheses and experiments it took them years to come up with (because they seemed to go against dogma in the field)3. 🔬 Why 'knowing too much' can be an obstacle to discovery in science, the beauty of an unbiased companion, piecing apart what they would have done differently if they'd had AI all along, and how José and Tiago will be using AI tools going forwardChapters00:00 Introduction: AI + phage research, and why we wanted to talk to José and Tiago!02:10 First, the biology background: exploring PICIs (phage-inducible chromosomal islands) and their significance10:13 The role of AI in hypothesis generation19:08 Interpreting data and overcoming bias28:40 Future implications of AI in phage therapy37:25 Experimental evidence and hypotheses validation40:46 AI tools and their effectiveness44:38 Interpreting AI outputs and experimental design51:30 The role of AI in scientific discovery57:30 Future of AI in research and collaborationPapers discussed:1. José and Tiago's new preprint on the science of PICIs: https://www.biorxiv.org/content/10.1101/2025.02.11.637232v1.full2. Their companion preprint on exactly how they worked with the AI co-scientist (+ benchmarking against other AI tools!): https://www.biorxiv.org/content/10.1101/2025.02.19.639094v1 More info about Google's AI co-scientist: https://research.google/blog/accelerating-scientific-breakthroughs-with-an-ai-co-scientist/More info about their research: José's lab: https://profiles.imperial.ac.uk/j.penades/aboutTiago's lab: https://profiles.imperial.ac.uk/t.costaWant to learn more about phage satellites? Check out this new Nature Reviews Microbiology by José's team: https://www.nature.com/articles/s41579-025-01156-z

"Somebody's father, friend, husband just passed away in the most developed country in the world... from a simple infection that probably could have been treated in Georgia." In this episode, we sit down with Dr. Alexander (Sandro) Sulakvelidze to explore his journey in growing a phage therapy company from scratch, from food to human therapy. Growing up in the Republic of Georgia, phage therapy was a normal thing for Sandro; when he came to the US and saw people dying of preventable infections, he founded Intralytix. This was 26 years ago. Takeaways: - Starting with food safety applications proved crucial for Intralytix's survival and success as one of the few profitable phage companies - The field has transformed from complete skepticism to active engagement, with hundreds attending phage conferences and multiple clinical trials underway - Current regulatory concerns about transducing phages may be disproportionate given natural background levels in the human gut - Personalized, customized phage cocktails consistently show better results than "mainstream" fixed cocktails - Modern healthcare lacks the infrastructure for phage therapy - there's no equivalent to antibiotic susceptibility testing - AI and machine learning are revolutionizing phage manufacturing, Intralytix is seeing 100% success in predicting optimal production conditions - The next 5 years may see limited adoption through personalized medicine and nutraceuticals, while mainstream adoption could take 15+ years - Phage therapy's future may extend beyond infectious disease to microbiome modulation for conditions like obesity and neurological disorders - Proof of efficacy in rigorous clinical trials remains the critical barrier to widespread adoption and insurance coverage - The field needs both mainstream products and the flexibility to customize treatments for individual patients Chapters: 00:00 Introduction to Phage Therapy and Background 06:01 Evolution of Phage Therapy and Regulatory Changes 11:51 Skepticism and Acceptance of Phage Therapy in the West 20:11 Challenges in FDA Approval and Transduction Concerns 26:09 Personalized Medicine and Future of Phage Therapy 35:36 Navigating Regulatory Challenges in Phage Therapy 38:31 Research Gaps and Future Directions 41:45 Infrastructure and Logistical Hurdles 44:31 The Need for Standardization in Phage Testing 46:15 Cross-Pollination Between Food Safety and Human Health 50:38 Future Outlook: Phage Therapy in 5 to 15 Years 57:07 Challenges Ahead: Efficacy and Regulatory Concerns Key Quotes: "Deep in my heart, there is no doubt this works. There's just too many successful stories." "My experience with FDA has been very good... The people we've dealt with have been reasonable." "The variables you have to examine are mind boggling... We use artificial intelligence to learn what creates the best conditions to grow each phage." "We are one of the very few phage companies today that actually has sales revenues... If you ignore the very long time, we're probably the only phage company that has some profit." "The customized cocktail always worked better... scientifically and technically, it has a better chance of working." Learn more about Intralytix: https://www.intralytix.com/

Welcome to the Podovirus podcast, episode 3! In this episode, I talk with Jesus Fernandez-Rodriguez from Eligo Bioscience, a Paris-based biotech company pioneering microbiome editing using modified bacteriophages. We talk about Eligo’s recent Nature publication, “In situ targeted base editing of bacteria in the mouse gut”, how it works, and what the team is thinking of doing with it. 💡 Takeaways: - Eligo Biosciences has developed a base editing technology using modified phages to precisely modify populations of E. coli and Klebsiella in the mouse gut microbiome without killing them. - Microbiome hype is not over yet! - Beyond using the editing tool to kill bacteria for therapeutic reasons, this tool can be used to delete a gene or bacterium to probe what happens in vivo, which could help us figure out what to try to drug next - Not all targets need to be infectious disease-based: the gut-brain axis is an interesting area that this approach could be useful for (or any bacteria-causing disease or phenotype) - The Eligo team designed their base editing system using a PICI (phage-inducible chromosomal island) origin of replication, which lets them produce their therapeutic 'cosmid' (plasmid containing lambda phage packaging instructions plus their payload) in an E. coli strain expressing PICI primase, but prevents replication of the cosmid in target bacteria. 📕 Read: Eligo's In Situ Base Editing paper, published July 2024 in Nature: https://www.nature.com/articles/s41586-024-07681-w 💻 Check out Eligo Bioscience's website, especially their open roles! https://eligo.bio/ Chapters 00:00 Introduction to Eligo Biosciences and their work 02:22 History and evolution of Eligo Biosciences' technology 03:23 Transition from antimicrobial focus to microbiome editing 05:21 Base editing, killing bacteria, and modifying bacteria 06:11 The importance of understanding and targeting bacterial genes in human disease 11:30 Distinguishing base editing from CRISPR and its applications 13:27 Different tools for different modifications in bacteria 16:16 Engineering phage particles for high transduction efficiencies 21:33 Challenges and process of publishing the paper 23:29 The value of publishing and attracting talent 27:19 Eligo Biosciences' plans for clinical trials and future applications 28:43 The importance of bacterial genes in human disease and the new way of thinking 29:12 Microbiome Research and Gut-Brain Axis 31:34 Challenges in Identifying Microbes and Genes 34:48 The PICI System in Eligo's Technology 37:14 Multiplexing the Base Editing Approach 52:04 Complexity of Identifying Disease-Causing Genes 56:25 The Importance of Research and Collaboration