Are Cell Therapies at an Inflection Point?

Breakthroughs in Cell Therapy Are Accelerating — Here’s Where Investors Should Look Beyond the Hype

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Hi! I’m Cristina. With roots in science and a track record leading strategy and partnerships across biotech, I focus on one thing: identifying breakthroughs that will make cell therapies mainstream—and invest before the world catches on.

Well, it finally happened. I’m putting my thoughts down - maybe not on paper, but out there. I’ll be honest, writing isn’t usually my thing. But I care deeply about where the field is headed, and I think this moment deserves more than a quick comment or LinkedIn post.

Spoiler alert, I believe a major shift is underway in the Cell Therapy space, one that will soon make these therapies mainstream options. What follows is my attempt to explain why.

A quick note before diving: for the sake of simplicity, I’m using “Gene Therapy” and “Cell Therapy” interchangeably here. I see Gene Therapy as a type of Cell Therapy, since the ultimate target of the intervention is the cell.

A Brief History of Cell Therapies

To me, the story of cell therapies begins with Rudolf Virchow, a 19^th- century doctor often referred to as the father of modern pathology. Rudolf’s cellular theory states that every living thing is made up of cells and every disease is the consequence of cells behaving incorrectly. No surprise, then, that some of the biggest blockbuster drugs of our time are built on the concept of manipulating cells. Keytruda binds to the protein PD-1 to help immune cells kill cancer cells better. Humira blocks TNF-alpha from attacking healthy cells and triggering inflammation. Ozempic helps regulate blood sugar by increasing cellular insulin secretion and reducing glucagon secretion. And there are others.

But the most elegant form of cell manipulation today is cell therapy. It’s a technology that uses the cell itself – through genetic modification - to produce a therapeutic effect. When you think about it, this isn’t just elegant, it’s transformative. It holds the promise of not just treating but curing some of the most devastating diseases of our time. If you’ve ever believed in the promise of medicine to not just treat, but truly cure, then cell therapies are likely already on your radar.

The concept of gene therapy was first introduced by Theodore Friedmann and Richard Roblin through a publication in Science on Mar 3, 1972. The field advanced steadily until the tragic death of Jesse Gelsinger in a clinical trial in the late 1990s. Jesse had a mild form of ornithine transcarbamylase deficiency, an X-linked genetic disease of the liver. The goal of the trial was to test the safety of using an adenoviral vector to deliver a corrected version of the gene. Tragically, Jesse experienced a massive immune response triggered by the viral vector, leading to his death. This event halted the field for nearly a decade. It was a devastating setback that forced important reflection and reform. Since then, we’ve learned a lot. Through immune modulation, smarter clinical trial design and patient selection, and more refined genetic engineering techniques, we’ve greatly reduced the risks of adverse outcomes like the one Jesse faced.

The transformative potential of cell therapies was uncovered, however, and the field picked up slowly but steadily soon after, culminating in the approval of Kymriah in 2017 for the treatment of pediatric patients and young adults with B-cell acute lymphoblastic leukemia (ALL). Since then, progress has accelerated at an incredible pace. Today, hundreds of people treated with cell therapies are on remission, and dozens of children, who received gene therapies, are not just surviving, they are thriving and living normal lives. The fact is that many people are alive and well today because of these remarkable medicines. The surge of global clinical programs, now expanding to more prevalent diseases, including neurodegenerative disorders, speaks volumes. There’s a shared urgency, and a growing belief, reflected in the record number of clinical trials and billions in investment, that we’re just scratching the surface of what these powerful medicines can do.

What’s Still Holding Cell Therapies Back?

Before we go any further, it’s important to clarify that cell therapies generally fall into two main categories: autologous and allogeneic.

In the autologous bucket, the therapy is tailor-made for an individual. To create an autologous cell therapy, the patient’s cells are first collected and sent to a centralized manufacturing facility. There, the cells serve as the raw material to produce the therapy. Once the product is manufactured and thoroughly tested, it’s released and shipped to a specialized treatment where it’s prepared and administered by highly trained physicians. Because this process is customized for each patient and typically involves a lot of manual handling, it introduces batch-to-batch variability, which can complicate development and regulatory approval.

As you can imagine, coordinating the logistics of autologous cell therapies is no small feat. Every step requires rigorous tracking, from the moment the cells are removed to the moment they are returned in therapeutic form. The entire process can take anywhere from several weeks to months and typically costs between $500K-$1M per patient in the US.

Access is another challenge. Since these therapies can only be administered in highly specialized centers, there’s a limited number of places where patients can actually receive treatment. The silver lining is that most autologous therapies are designed to be “one-and-done”. At least 13 highly efficacious autologous therapies have been approved in the U.S. to date.

Autologous therapies just aren’t scalable. They require too much time, money, and specialized infrastructure to be practical at large scale, especially for diseases that impact thousands of people.

This is where allogeneic approaches come in. These are often referred to as “off-the-shelf” therapies, meaning they’re designed to be mass produced and administered to any patient who shares a particular disease or mutation. All currently approved allogeneic therapies are administered in vivo (directly into the patient) and without the need to collect and process the patient’s own cells. This simplifies logistics quite a bit. While the supply chain is simpler compared to autologous approaches, approved therapies today still rely on complex manufacturing, involving viral vectors as the active ingredient. Viral vectors are manufactured using cell-based technologies that can also be very costly. Further, these vectors must be extensively characterized to prevent unwanted immune responses. Manufacturing viral vectors is no easy task and there is a need to produce large amounts, even when treating small populations. It’s worth noting that all nine currently approved allogeneic gene therapies are for rare diseases.

The Science is there. The Engineering is catching up.

Here’s where the shift becomes real. If you’re an optimist (and a realist) like me, you can probably see the enormous potential to simplify the complexity of everything we just walked through. The ultimate goal is to make these therapies not only more accessible and cost effective but also scalable enough to reach a much broader range of patients. Because let’s be honest: the potential isn’t limited to a niche. These therapies could one day benefit nearly everyone.

From automation and closed-system manufacturing to reducing the need for highly specialized treatment centers, there are major opportunities to streamline how these therapies are made and delivered. AI tools are also starting to play a bigger role in improving product characterization, optimizing manufacturing workflows, or managing supply chains more efficiently. Advances in delivery technologies and new off-the shelf approaches are expanding the scope of who can benefit and making it increasingly feasible to treat more common diseases.

The opportunity ahead is immense but the window to shape how it unfolds is closing fast. The field is quickly catching up, and those who move early will help define what “mainstream” really looks like.

Companies to Watch

A big reason I wrote this piece is to spotlight a few companies that, to me, represent the kind of progress that could make cell therapies mainstream. Each is taking a different approach, but all are solving real challenges in innovative ways worth paying attention to.

Fuse Vectors. You might be wondering why viruses are the go-to tools for gene and cell therapies today. It’s because viruses are naturally great at delivering genetic material into cells, and we’ve gotten pretty good at engineering them to carry and express whatever protein we want. Viral envelope proteins interact with specific receptors on the surface of cells, kind of like a key fitting into a lock, allowing them to sneak in and do their job. One of the most widely used viral vectors is the adeno-associated virus (AAV). AAVs are especially efficient at delivering genes to the liver, muscle, retina, and central nervous system (CNS). But while they work well biologically, manufacturing them is a different story. The process is complex, cell-based, and often leads to a mix of full, empty, and partially filled capsids, which adds a layer of variability and cost that’s hard to control. That’s why I’m really excited about what Fuse Vectors is doing in Copenhagen. They’re building a cell-free manufacturing platform for assembling AAVs, which could significantly cut down on cost and improve consistency. It’s a much-needed innovation in the field.

GC Therapeutics. I’m excited about GC Therapeutics - not just because it’s a spin-out from George Church’s lab (yes, that’s George Church: renowned scientist, prolific entrepreneur, and co-founder of Colossal, the company bringing back the wholly mammoth and dire wolf) - but because Induced Pluripotent Stem Cells (iPSC) represent the next frontier of cell therapies.

Fun fact: There’s talk that the company may have even used George Church’s (“GC”) skin cells to generate iPSCs. Whether or not that’s true, it’s a great story and a nod to the science forward ethos of the company.

iPSCs can be differentiated into virtually any cell type, they hold huge potential as off-the-shelf treatments for a wide range of diseases. But directing iPSC to become a specific cell type isn’t trivial. It depends on activating the right combination of cell pathways and transcription factors. That’s where GC Therapeutics’s TFome platform comes in. It helps identify the precise cocktail of transcription factors needed to reliably guide iPSC into a desired cell type, making scalable, consistent manufacturing of these therapies much more achievable.

CircNova. Let’s talk about circular RNAs for a minute. We’ve known about covalently closed circular RNAs since the 1970s, but for decades they were dismissed as byproduct of mRNA splicing, not important enough to pay much attention to. That changed in the 2010s, when three separate publications showed that these so-called “non-coding” RNAs were actually capable of protein expression.

Unlike traditional mRNA, circular RNAs form a closed-loop structure and lack free ends, making them much more resistant to degradation. That gives them a major advantage when it comes to stability. CircNova, a startup out of Detroit, picked up on this early. They’re advancing an AI-driven platform called NovaEngine to design, analyze, and identify circular RNAs for therapeutic use. Think of NovaEngine as the RNA version of AlphaFold, predicting how these RNAs fold, and behave to guide therapeutic design. Because of their enhanced stability and lower immunogenicity, circular RNAs hold huge promise for creating durable responses, potentially improving viral vector delivery by reducing dosing requirements – which could make gene therapies both safer and more affordable. Interest in the space is definitely heating up with a Chinese stealth company recently announcing their first clinical trial using circular RNAs. I see growing momentum around CircNova. They are absolutely one to watch.

Looking Ahead

I really believe the field is shifting and companies like the ones described above are leading the way. They’re pushing boundaries with innovative approaches to reducing costs, expanding access, and showing what’s possible. I’ll definitely be keeping a close eye on them.

If this sparked ideas or challenged your thinking, I’d love to hear your perspective. Where do you see the field going, or what opportunities do you think could open up if these companies succeed? I’m happy to share deeper takes or connect you with others working in this space, just reach out!