For most of the past decade, gene therapy’s big promise came with an awkward catch: getting the genes where they need to go. Viral vectors can miss their target tissue, ex vivo cell therapies require weeks of custom manufacturing for each patient, and many editing tools can only make small fixes, one mutation at a time. Those limits have kept many potentially transformative treatments expensive, hard to make, and out of reach for most of the people who could use them.
In 2026, dealmakers went after that bottleneck directly. The year’s largest gene therapy transactions went to companies building ways to engineer cells inside the body, insert whole stretches of DNA at precise sites, and send therapies into the eye with a simple injection in a doctor’s office. Eli Lilly and Company led the charge with three of the five deals below, part of a broader genetic medicine push that included opening a dedicated research center in Boston.
At the other end of the market, a late-stage Fabry disease program came out of a bankruptcy auction with a new owner. That deal is a reminder that strong clinical data doesn’t guarantee the developer survives to bring the therapy to market.
The deals below are ranked by total disclosed value and cover DNA-based gene therapy and gene editing. Lilly’s $2.4 billion acquisition of Orna Therapeutics sits just outside that scope, since Orna’s platform runs on circular RNA. Even so, it shows how much Lilly is betting on in vivo medicine.
1. Eli Lilly acquires Kelonia Therapeutics
Lilly agreed to acquire Kelonia Therapeutics, a Boston-based company specializing in in vivo gene delivery, for $3.25 billion upfront and $3.75 billion in milestone payments. Kelonia’s in vivo gene placement system uses engineered lentiviral-based particles that deliver T cells inside the body, so the patient’s own body generates chimeric antigen receptor (CAR) T cells. The approach could remove ex vivo, patient-specific manufacturing, and pretreatment chemotherapy from the process.
The lead program, KLN-1010, is a one-time intravenous gene therapy that generates CAR T cells against B-cell maturation antigen on multiple myeloma cells. It is in a Phase 1 clinical trial. Jacob Van Naarden, President of Lilly Oncology, called the early clinical data “highly encouraging,” in a press release.
2. Eli Lilly partners with Profluent
Profluent, an AI-focused protein design company, announced a multiprogram partnership with Lilly. Under it, Profluent will use AI to design custom recombinases that target exact genomic locations for large-scale, precise DNA editing. The goal is to insert long stretches of DNA, sometimes entire genes, at precise sites. That would let a single therapy cover many mutations in the same gene.
The companies did not disclose the upfront payment, the number of programs, or the target diseases. If every program succeeds, Lilly would pay $2.25 billion in milestones. Lilly recently opened a genetic medicine center in Boston.
3. Eli Lilly licenses Seamless Therapeutics’ recombinases
Seamless Therapeutics signed a research collaboration and licensing agreement with Lilly to develop programmable recombinase-based treatments for hearing loss. Its technology makes large, precise DNA insertions in any target gene sequence and works independently of the cell’s natural DNA repair pathway.
Seamless will design recombinases that correct mutations in selected hearing loss genes, and Lilly receives an exclusive license to take them through development and commercialization. Seamless receives a guaranteed upfront payment and committed research and development funding. In total it is eligible for more than $1.12 billion, plus tiered royalties.
4. Ikarovec takes an option on VectorBuilder’s eye capsid
UK-based Ikarovec, which develops dual-pathway gene therapies for retinal diseases, secured an exclusive worldwide option on an adeno-associated virus capsid from VectorBuilder. The capsid will be used for IKAR-003, a preclinical gene therapy for intermediate age-related macular degeneration. VectorBuilder built the capsid with its AI-based DeepCap platform, and it reached broad areas of the retina in nonhuman primate studies after intravitreal injection. That route would allow delivery in a doctor’s office.
If further evaluation goes well, the companies will form a strategic partnership in which Ikarovec handles clinical development and commercialization. The proposed deal is expected to be worth more than $1 billion.
5. PTC Therapeutics wins Sangamo’s Fabry disease gene therapy
PTC Therapeutics won a bankruptcy auction for ST-920, a one-time adeno-associated virus gene therapy for Fabry disease, from Sangamo Therapeutics during Sangamo’s Chapter 11 case. The therapy is designed for long-term production of alpha-galactosidase A, the enzyme people with Fabry disease lack, and could ease the burden of chronic enzyme replacement therapy.
PTC paid $111 million upfront plus up to $100 million in contingent milestones. The winning bid was more than four times Astellas’ original stalking-horse bid. PTC completed the acquisition in September and expects to finish its rolling biologics license application for accelerated approval in the fourth quarter of 2026. The program holds Regenerative Medicine Advanced Therapy, Orphan Drug, and Fast Track designations.
All of these deals highlight major engineering progress for gene therapy, and signal continued growth that investors and drugmakers alike will have to keep an eye on in 2027.
