The European Society of Gene & Cell Therapy (ESGCT) has become the epicenter of what’s next in biotech: where the most audacious ideas in cell and gene therapy come to play before they hit the clinic.  

This year we were lucky enough to have it in beautiful Sevilla, with all the right ingredients (aside from the best tapas): viral engineering, RNA re-writing, in vivo CAR-T innovation, and even cellular rejuvenation pushing the boundaries of longevity. 

If the last decade was about proving that genetic medicines can work, 2025 is about re-programming biology itself: moving from cutting and adding genes to editing, tuning, and rejuvenating them. 

Here’s what stood out to us from four days of scientific overload: 

1. From one-shot cures to programmable platforms 

Across sessions, a clear theme emerged: the future isn’t just about fixing one gene at a time, but rather building modular, re-usable platforms that can write, silence, or boost expression in a controlled way. 

Whether through engineered viral vectors, RNA-based systems, or synthetic circuits, researchers are finding ways to make therapies more flexible, reversible, and tissue-specific.
The next frontier of gene therapy looks much more like software: editable, easy to update, and adaptable to each patient. 

2. RNA is the new playground 

New approaches are turning RNA into a programmable material for therapy: from temporary gene editing and exon rewriting to synthetic RNA that can fine-tune protein levels. 

Many of us dream on a soon reachable broader tissue reach, fewer safety issues, and scalable manufacturing.
RNA might just become the medicine itself, and not only the messenger. 

3. Smarter, safer immune cells: CAR-T, CAR-NK, and the allogeneic arms race 

The cell therapy field is evolving fast.
The spotlight has now shifted to engineering persistence, control, and affordability.
Off-the-shelf NK cells, dual-target CARs, and other hybrid designs all point toward more robust and accessible treatments.
The next generation of cell therapies must be designed not just for power, but for scalability and accessibility. 

4. Aging, reprogrammed 

Longevity science made a quiet but powerful entrance.
Partial cellular reprogramming and epigenetic rejuvenation are showing early evidence of restoring tissue function and slowing disease.
The concept is shifting from idea to therapy: helping cells stay young to prevent illness.
It’s early, but it could redefine what “advanced therapy” means in the next decade. 

5. Viruses reinvented 

Oncolytic and viral vectors are making a comeback. But this time as immune trainers, not just delivery tools. By combining viral delivery with immune activation, researchers are teaching the body to recognize and attack tumors. 

This new wave of viral therapeutics blends the best of immuno-oncology and gene therapy: from “infectious” to “instructive”.  

6. CNS: gene therapy for the brain is finally advancing 

For a long time, treating the brain was one of the biggest challenges in medicine.
This year, new vectors, editing tools, and cell-based approaches showed that it may finally be possible to reach the brain effectively and safely. 

The potential impact goes far beyond rare diseases, and it could open new options for pediatric, neurodegenerative and cognitive disorders that were once untreatable. 

The big picture 

Walking out of ESGCT 2025, one message stood out: we are moving from therapy to programmability. 

• Biology is becoming editable at every level: DNA, RNA and even the epigenome.  
• The line between curative and regenerative is fading. 
• The next winners will be those who combine precision with flexibility, building tools that evolve with science itself.

Investor Takeaways 

• Platform over product: Investors are looking beyond single-gene cures toward modular platforms that can address multiple diseases with one core technology. 
• Delivery is still king, but precision is queen: AAV innovation continues, but the most exciting developments involve how precisely we can regulate and localize genetic activity. (at tissue and cellular level). 
• RNA is the next investment wave: It’s versatile, re-dosable, and increasingly manufacturable at scale. 
• CNS and aging are coming of age: Once considered uninvestable, both are now ripe for early bets as new delivery and reprogramming data accumulate. 
• Integration will define winners: The future belongs to teams combining biology, computation, AI, and engineering: the ones who can treat cells as programmable systems.

SYNTHETIC BIOLOGY FUTURE DIRECTIONS / Synthetic Biology offers new ways for engineering new biological systems or re-designing existing ones for useful purposes. It is a disruptive technology at the heart of the so-called Bioeconomy, capable of delivering new solutions to global healthcare, but also in many other fields like agriculture, manufacturing, and environmental challenges. Not long ago, in May 2010, a team of scientists led by Craig Venter achieved a synthetic biology milestone by designing the genes for a new type of bacteria and implanting them in a bacterial shell that had its genome removed. The empty cell behaved like a factory programmed with human-designed genetic code. It was the first living being to escape the evolutionary tree, with a computer-programmed genome synthesized by chemical compounds, implanted in a cell, and subsequently multiplied under the control of that artificial genetic code. It opened the way to extraordinary developments in biology and medicine that are starting to blossom now. But we have a lot of work ahead. This quick_note tries to systematize the progressive steps in our quest to design “therapeutic life” #quick_notes_lp

Retinal diseases remain a difficult problem to solve because (1) the retina is in a sense a biological computer that needs to be properly “rewired”, (2) animal models are poor because they have no fovea, (3) the internal limiting membrane (ILM) limits delivery, and (4) regeneration of mammalian retinal is absent. However, very promising strategies are emerging, here is a conceptual map of the most interesting approaches to solve the problem. #quick_notes_lp

Solving real problems requires commitment and focus. Here’s some advice for scientists willing to become entrepreneurs, six things you should think about before embarking on your journey: (1) UNDERSTAND BIOTECH ECOSYSTEM/ Be aware of what creates and what destroys value, and understand why VCs prefer good problems to solve, big clinical needs, accelerated regulatory pathways and a big delta in what the drug will do for patients: USE IT TO IMPROVE YOUR POSITIONING (2) UNDERSTAND YOUR COMPANY/ Ask yourself what open questions still remain unsolved in your field (they’ll lead you to clinical needs), and see the landscape of strategies to solve your particular clinical need: are you competitive enough? STAND OUT FROM THE CROWD (3) FROM SOLOIST TO ORCHESTRA/ Find the right CEO (maybe yourself, but some other times someone else more experienced) and the right team that will make it possible… At first the team will be small but always bear in mind entrepreneurship is not an individual game (4) CONTACT YOUR TECHNOLOGY TRANSFER OFFICE (research center, hospital…) or alternatively experts and consultants to think carefully about the whole process, the intellectual property, some initial understanding of the regulatory pathway, license negotiations to spin out, etc. (5) FINE TUNE PoC/ Find your WOW slide, the experimental setting and results that will convince everyone that this is worth doing and that your way of solving the problem actually works… You’ll probably need to further improve it after visiting VCs, yes, but always aim for top quality experiments (6) FUNDRAISE / Go find capital (non-dilutive from grants first, if possible), understand how VCs will analyze your project and try to capture their attention. The process iterates non-stop, go back to (1) to further understand your sector and start again to perfect your pitch.

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Glioblastoma remains one of the most pressing clinical needs in medicine. Its prognosis is dismal and current standard of care involves maximal safe surgical resection, radiotherapy and chemotherapy. News drugs are on the way though: many groups across the world are trying to solve the challenge. It is indeed a difficult challenge because (1) the blood brain barrier limits PK/PD, (2) new studies confirm glioblastoma stem cells confer resistance, (3) clinical trials are usually done in recurrent patients, and (4) no monotherapy strategy will probably eradicate it completely. It is a especially dear field to me because as some of you may know I used to operate them as a former neurosurgeon and I’ve seen first-hand how aggressive they are.
All big unsolved clinical needs may be a good investment opportunity. Here’s a conceptual map with some of the leading-edge alternatives and targets that are being moved forward.
You can find all my quick notes at #quick_notes_LP

The higher the clinical need and the prevalence, the higher the effort from scientists around the world in trying to solve a problem. Pancreatic ductal adenocarcinoma (PDAC) remains one of the highest unsolved clinical needs today. It is a devastating disease with an unfavorable outcome and is projected to become the second deadliest cancer by 2030. Currently the overall 5-year survival rate is less than 10% despite all efforts. But new therapies are being pushed forward every month, the rhythm of innovation here is extraordinary.
All big unsolved clinical needs may be a good investment opportunity. Here’s a conceptual map (by no means complete) with some of the leading-edge alternatives and targets that are being moved forward. A map just to navigate the landscape and avoid getting lost amid all the different categories and approaches.
You can find all my quick notes at #quick_notes_LP

Some advice for scientists willing to become entrepreneurs, here are six things you should think carefully before embarking on your journey… (OPENING THREAD: some slides I used in a lecture @EU_Commission last month)

#quick_notes_LP

Here’s a map of some of the most promising research fields in oncology today, plus a video —below— with some advice for scientists willing to become entrepreneurs (from a debate on the future of oncology and how to make it happen)

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One of the most important things every investor looks for in a startup is a good problem to solve… Unanswered questions always signal what’s next. Here’s a map of some of the most pressing questions in the oncology field today.

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RNAs are very active players in cell biology… they carry instructions for making proteins, turn genes on and off, aid chemical reactions, slice and dice other RNAs, and build proteins. Here’s a simple map to understand how can we use them as drugs

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A different view on phase II – III #COVID_19 vaccines, organized on a spectrum ranging from less innovative technology (older, slower, less uncertain development) to more leading edge approaches (faster, riskier)

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You already have a lead candidate for a first specific indication, here’s a simplified conceptual map on how VCs think to choose the most interesting new indications (pipeline strategy).

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Every crisis brings risks and opportunities to the table… here’s a mind map on how SARS-CoV-2 can impact the activities and value chain of the life sciences VC industry

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Most rare diseases still lack approved treatments despite major advances in the knowledge of their molecular basis. Here’s a map of the different therapeutic modalities plus an update on some of the most interesting new developments in each field.

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The vaccine effort for #COVID19 is unprecedented in scale & speed. To get it right and fast we need new tools and strategies including DNA/RNA vaccines, virus-like particles, T-cell inducing peptides & viral vectors… here’s a map of the leading edge

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