Gene editing has fluctuated between promise and reality for a decade. At the 2026 J.P. Morgan Healthcare Conference, that tension hadn’t dissipated, but the tone had shifted. This year’s biggest updates weren’t about platform power or hypotheticals. Instead, they were rooted in clinical data, manufacturability, access, and, most critically, business success.
In these video interviews, I met with the brass of four gene editing companies—Mammoth Biosciences, Caribou Biosciences, Stylus Medicine, and RheumaGEN—each offering different but interconnected solutions, each attacking a distinct bottleneck on the path from elegant edit to broadly accessible therapy.
Trevor Martin (co-founder and CEO Mammoth Biosciences)
Mammoth Biosciences, a spinout from the lab of Nobel Prize laureate Jennifer Doudna, PhD, was put on the map for its CRISPR-based diagnostics, including pandemic-era COVID testing. But the company has been searching for its north star, with hands in diagnostics, therapeutics, and protein design. There were indicators that Mammoth had narrowed its focus to therapeutics, and right before this year’s J.P. Morgan Healthcare Conference, Mammoth made a company-defining announcement, revealing its first clinical program. So, why did it take so long to make this decision and what went into it?
CEO Trevor Martin, PhD, explained that instead of chasing crowded targets, Mammoth leveraged its position as a “second mover” in treating liver diseases, a battleground for companies using lipid nanoparticles (LNPs) to deliver cargo that preferentially targets the liver. Their analysis led Mammoth to APOC3, a gene that when knocked down dramatically lowers triglycerides and addresses severe conditions, such as familial chylomicronemia syndrome and severe hypertriglyceridemia. While triglycerides were long dismissed as a niche market, Mammoth saw millions of potential patients—and a rare opportunity for a one-time, potentially permanent solution where small molecules and antibodies have repeatedly fallen short. The result is MB-111, which the company expects to enter the clinic this year, with the goal of normalizing triglycerides for life.
Beyond the liver program, Martin emphasized Mammoth’s broader platform of ultra-compact CRISPR systems capable of extrahepatic delivery to tissues like muscle and brain. That platform breadth creates opportunity—but also tension. While it enables smarter target selection and partnerships, including working with Regeneron, today’s market rewards clinical proof points more than long-term optionality. Balancing those forces, Martin argued, is essential to building a “generational” biotech rather than a single-asset story. CRISPR’s progress has been slow and incremental, Martin acknowledged, but the inflection is approaching liver first, then muscle and brain, and eventually a world in which many genetic diseases are no longer accepted as inevitable.
Rachel Haurwitz (co-founder and CEO Caribou Biosciences)
Rachel Haurwitz, PhD, co-founder and CEO of Caribou Biosciences, founded the company as a next-generation CRISPR company built not on re-engineering Cas enzymes, but on rewriting the rules of guide design. But Caribou, another Doudna lab spinout, focused its flagship innovation on dramatically improving editing specificity by modifying the guide molecule itself. Caribou’s chRDNA (CRISPR hybrid RNA-DNA, pronounced “chardonnay”) is a shift that Haurwitz argued unlocks something the field has long struggled to achieve: the ability to make multiplex and complex edits safely. That capability underpins Caribou’s lead program, Vispa-cel, designed to solve the fundamental flaw that doomed earlier off-the-shelf efforts for CAR T cell therapies via three CRISPR genome edits. In addition to insertion of the CAR, Vispa-cel has two deactivating edits: one targets the T-cell receptor, and the second targets PD-1 to repress inhibitory signaling that limits tumor activity.
But for Haurwitz, the significance of allogeneic CAR T is less about technological elegance than access. Today, only about 25% of second-line lymphoma patients ever receive autologous CAR T, constrained by manufacturing delays and concentration at elite academic centers. Caribou’s freezer-ready product can be administered immediately and deployed in community hospitals, reaching patients who are too sick to wait or unable to travel. Caribou put this to the test in a Phase I trial for Vispa-cel, treating 84 patients with the therapy from over 10 different batches. The initial results, reported in November 2025, showed response rates, complete responses, and, importantly, lasting effects of Vispa-cel similar to those of approved autologous CAR Ts.
An added benefit to the off-the-shelf strategy is that the cell therapy uses cells from healthy donors and not those battered by cancer and chemotherapies for years, eliminating variability in efficacy using the autologous CAR T approach. Caribou has a planned pivotal Phase II trial for Vispa-cel in autologous CAR T and transplant-ineligible second-line patients (roughly 60% of the population) in a randomized study against chemo-immunotherapy. Beyond lymphoma, a BCMA-targeted allogeneic CAR T for multiple myeloma is showing early dose-expansion data approaching autologous-like efficacy in a far larger and more underserved population. With batch manufacturing, stockpiling, and an estimated 96% lower cost of goods than autologous CAR T, Caribou’s platform represents a rare convergence of clinical parity, scalability, and commercial viability.
Emile Nuwaysir (CEO Stylus Medicine) and Jason Fontenot (CSO Stylus Medicine)
Emile Nuwaysir, PhD, CEO of Stylus Medicine, similarly framed the nearly four-year-old company around the accessibility failures of ex vivo CAR T cell therapy. Over the course of 15 years, CAR T has successfully treated approximately 40,000 patients, while tens of millions have received cancer diagnoses. Stylus was built to close that gap by transforming CAR T from a bespoke, multi-week procedure into an in vivo, vaccine-like therapy capable of reaching millions.
The scientific foundation, Nuwaysir argued, is already in place. More than a decade of clinical experience has validated CAR design, safety management, and patient selection. What remains broken is the business model. What is most distinguishing about Stylus Medicine is that the company is leaving the CRISPR sandbox for a different gene editing technology. CSO Jason Fontenot, PhD, detailed how Stylus plans to do it: a highly engineered, phage-derived recombinase that enables precise, single-step insertion of large genetic payloads without creating double-strand DNA breaks. Combined with targeted lipid nanoparticle delivery to circulating T cells, the platform enables durable, nonviral genetic engineering at scale—a “best of both worlds” approach to the company called LNP-durable.
The result is the potential for far more sophisticated cell engineering, essential for solid tumors and autoimmune disease, without the cost and complexity of viral vectors. With strong preclinical data and plans to finance through initial human clinical readouts this year, Stylus is entering a rapidly heating in vivo CAR T landscape where pharma is already placing multibillion-dollar bets. Stylus’ vision to translate that proven biology into a simple, community-delivered in vivo paradigm could be an inflection point not just for CAR T, but for cell and gene medicine as a whole.
Richard Freed (co-founder and CEO RheumaGen)
After a decade at DuPont translating lab inventions into scalable products, Richard Freed reconnected with his uncle, Brian Freed, PhD, who runs a hospital-integrated immune cell and gene therapy lab at the University of Colorado. That lab’s clinical HLA typing and transplant work funds the research that ultimately spun out RheumaGen, with the Freed nephew taking on CEO and the uncle Freed CSO.
According to the RheumaGen CEO, the company’s central insight is deceptively simple: many autoimmune diseases are driven by a small set of “bad actor” HLA alleles that mis-present self-antigens to T cells. Rather than pursuing disease-by-disease solutions, RheumaGen identified a single shared “anchor edit” across HLA molecules that prevents pathogenic peptide binding, which the CEO described as “breaking the bottom of a zipper,” while leaving the rest of immune function intact. Because patients carry many HLA alleles, modifying one is unlikely to cause meaningful immunosuppression, and mild conditioning regimens could allow outpatient treatment.
RheumaGen will start ex vivo editing patient cells in Colorado to prove safety and efficacy in refractory rheumatoid arthritis, with an IND expected by the end of 2026 and first patients in early 2027. But the long-term ambition is in vivo, enabled by a partnership with CIViC Biotechnology and its bacterial BactPac delivery platform. Produced via fermentation rather than viral-vector manufacturing, the BactPac could drive costs down from hundreds of thousands of dollars per patient to the low hundreds. For the CEO, the pivot—pausing to consolidate around a single universal edit and a radically simpler manufacturing model—reflects growing investor and payer scrutiny of gene therapy economics. With rheumatoid arthritis affecting roughly one percent of the global population, RheumaGEN is betting that a scalable, platform-style approach can reset immune “factory settings” across multiple diseases.
Novelty no more
Taken together, these conversations suggest gene editing is entering a more mature and demanding phase. Novelty alone no longer commands a premium. Just look at the increasingly competitive allogeneic CAR T space, which, in addition to Vispa-cel, includes CRISPR-edited approaches like CTX-112 (CRISPR Therapeutics) and other allogeneic CAR T technologies (i.e., Allogene and TALENs, Precision BioSciences and ARCUS). Even Stylus isn’t the only company with in vivo CAR T programs, with some reports estimating over 30 such programs. What matters now is whether these technologies can be viable for commercial first-in-class therapeutics.
But at JPM 2026, gene editing no longer looked like a science searching for a business model. It looked like a sector collectively and finally learned how to become medicine.
