Cells are a remarkable unit of life. They carry the ability to reproduce, to grow into tissues and organs, to sense and respond to their environments, to store and use energy, and to manufacture and secrete products of many kinds throughout the body. They have evolved enormous complexity, well beyond our capacity for de novo design. It is not surprising, then, that in many human diseases, when our cells are depleted or aged or not functioning, cellular medicines—delivering new cells back to the body—might offer the most logical and the most comprehensive form of therapeutic intervention available.
Scalable cellular medicines: the holy grail
Cell therapy is indeed a holy grail that has captivated the field of regenerative medicine for decades. New neurons for neurodegenerative disease, new cardiomyocytes for heart failure, new hepatocytes for liver failure, new retinal cells for blindness…the list of potentially game-changing medicines is long.
But where will the cells come from? While bone marrow transplants and autologous CAR-T therapies are of course now widely used therapies, in most diseases, the patient’s own cells are not a feasible cell source, and for most cell types, no scalable sources of donor cells exist either.
In 2007, a team of scientists in Japan famously discovered methods (now dubbed the “Yamanaka factors”) to create induced pluripotent stem cells (iPSCs) from adult human cells. They showed that these iPSCs mimicked the properties of human embryonic stem cells: they were self-renewing, and pluripotent. iPSCs could then, in principle, differentiate into a scaled supply of many specialized human cell types. This groundbreaking discovery led to the establishment of stem cell research centers all over the world, the creation of master iPSC cell banks, and a flurry of research describing how to coax iPSCs into a variety of therapeutically relevant cell types.
Still, nearly 20 years later, no iPSC-derived cellular medicines have yet been FDA-approved. While several exciting clinical trials have now demonstrated promising results (e.g., Vertex / Semma in type 1 diabetes; BlueRock in Parkinson’s Disease), precise methods for the differentiation of most human cell types remain either unknown, not reproducible (even necessitating new research standards), fundamentally unscalable, or prohibitively expensive.
Bringing technology to the task: GCTx and TFome™
Transcription factors (TFs) are powerful “master regulators” inside the cell, directing the cell’s machinery to express certain genes, and keep others turned off. During development, TFs are known to play a key role in determining cell ‘fate,’ and driving differentiation of stem cells into more specialized cell types. The status quo for iPSC differentiation research, therefore, has been focused on hypothesis-driven approaches to testing the role of different TFs, at different timepoints, in different artisanal lab protocols. But there are thousands of TFs in the cell—the space of possible differentiation protocols is simply too large to manually traverse with only ‘educated guesses.’
GCTx is flipping the entire iPSC differentiation paradigm on its head. Rather than manually iterating through a limited set of differentiation protocols, the Human TFome technology platform instead deploys large-scale combinatorial screening to discover new hypotheses and better methods that are as-yet unknown to even the best biologists. Importantly, TFome screening is fundamentally unbiased, and unshackled by prior knowledge—and could instead blow open new biological insights regarding how best to differentiate and develop different cell types of interest.
Every day, GCTx is discovering previously unknown cocktails of transcription factors whose exposure to iPSCs can induce rapid differentiation into many different cell types of interest. These cocktails are then refined, optimized, and further tailored to produce precise cellular phenotypes. And differentiated cells can then be further engineered (into what GCTx calls “SuperCells”) in a variety of ways to improve their ability to modify disease, engraft into the human body, avoid immune rejection, etc.
When we first heard the GC Therapeutics pitch, the opportunity to build a suite of truly “off the shelf” (e.g., scalable, not patient-specific, accessible to all) cellular medicines for a wide range of diseases caught our eye. The cell therapy industry is in need of more capital- and time-efficient approaches, and GCTx promises to deliver exactly that. The early differentiation protocols identified by TFome can produce differentiated human cells in a single-step, four-day process—in sharp contrast to many current iPSC differentiation protocols which can take weeks or even months to complete.
Scientists, entrepreneurs, and company builders
Translating a technology platform initially developed in academia into a flourishing biotech company with a therapeutic product pipeline is a tall feat. Over the last several years, this is exactly what GC Therapeutics’ co-founders Parastoo and Alex have done.
Parastoo and Alex first met at Harvard University in George Church’s lab, when they were united by their ambition and undeterred-by-challenge personalities. Parastoo had previously trained in bioengineering, co-founded a company called Tympanogen Inc, and co-invented a technology that later went into a company called AxoSim. Alex had trained in biochemistry and statistics, and developed deep expertise in synthetic biology. Shortly after starting GCTx together, Parastoo and Alex earned a flurry of recognition from many groups: grants from the Harvard Biomedical Blavatnik Accelerator, the Massachusetts Life Sciences Innovation Day Prize, Golden Tickets from Amgen and Biogen, honors in the Harvard President’s Innovation Challenge, and even a highlight on CBS’s 60 Minutes.
As great founders do, Parastoo (CEO) and Alex (CSO) channeled this early momentum into recruiting a phenomenal team and advisors to the company. In Albert Claude’s words—if cells are the units of our body creating a will to survive and thrive…then the members of GCTx’s team are the units of the company driving forward a culture of rigor and excellence. We have found them to be meticulous about every technical and regulatory detail, but also intensely focused on their long-term goal to develop impactful medicines for patients in need.
It has been a pleasure serving on the GCTx board and witnessing the company’s tremendous progress through Seed and now Series A financing. I’ll never stop gazing with awe at the stunning microscopy images we are generating of cells differentiated in our labs (they are framed on my walls…).
The GCTx team is hiring!
