7 Biotechs Fighting Rare Diseases With Gene-Editing Tech

Rare diseases sit at an uncomfortable scale: about 30 million people in the U.S., roughly >300 million worldwide. According to NIH, there are an estimated 6,000 to 8,000 rare diseases, though the exact number is continually changing as new conditions are identified. According to the 2024 Lancet publication, an estimated 95% have no FDA-approved treatment.

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In the U.S., a rare disease is defined by law as a condition affecting fewer than 200,000 people; in the EU, the threshold is a prevalence of no more than 1 in 2,000. Collectively, rare diseases remain a major unmet-need area despite progress in gene transfer and editing modalities.

According to the 2019 paper published in the European Journal of Human Genetics, more than 70% of rare diseases have a genetic cause, which is why genome-targeting approaches have become central to new drug pipelines. Moreover, about 70% are exclusively pediatric onset. Since late-2023, the field crossed a regulatory milestone with the first U.S. approval of a CRISPR-based therapy for sickle cell disease, followed by approval for transfusion-dependent beta-thalassemia in 2024.

In September 2025, the FDA proposed a Rare Disease Evidence Principles process to speed reviews for ultra-rare genetic conditions—generally populations under ~1,000 in the U.S.—when no adequate disease-modifying options exist. Under the proposal, “substantial evidence” could often be met with one adequate, well-controlled study (which could be a single-arm trial) if backed by confirmatory evidence such as target engagement and relevant preclinical data. The aim is to adapt evidentiary standards to the realities of very small cohorts while preserving rigor. 

However, these conditions still remain stubbornly hard to treat: diagnosis often arrives late, patient groups are tiny and geographically scattered, and the biology can splinter into many genetic subtypes even within a single label. That forces programs to make hard choices—ex vivo versus in vivo editing, AAV versus LNP delivery, liver-first versus extrahepatic targets—each with trade-offs in durability, re-dosing, and immunogenicity. 

In this article, we will outline a list of notable companies using gene editing and adjacent genome-engineering approaches against rare diseases—focusing on clinical readouts, delivery choices, financing, and partnerships.

Generation Bio

In many autoimmune conditions, misdirected T cells set off and sustain the tissue-damaging cascade. If one can quiet the specific gene signals inside those T cells, one can blunt the attack at its source while leaving the rest of the immune system largely intact. 

Generation Bio is building a delivery system that treats T cells like a precise mailing address. Its cell-targeted lipid nanoparticles (ctLNPs) carry short strands of RNA (siRNA) that switch off chosen genes inside T cells, the immune cells that drive many autoimmune and rare inflammatory conditions. 

A “stealth” surface keeps the particles from sticking to blood proteins and avoids rapid pickup by the liver and spleen so more of the dose reaches the intended cells. Uptake happens only in cells that display the right receptor, which means knockdown in T cells without hitting other immune or blood cells. Inside the cell, the particles are engineered to release siRNA into the cytoplasm where it can work, something direct drug conjugates struggle to achieve. 

The platform is modular: swapping the surface ligand retargets new cell types, and the core can carry a range of nucleic-acid payloads. For hard-to-drug T-cell targets this opens a path to redosable, tuned gene silencing with a wider safety margin, aiming to adjust how T cells activate, differentiate, migrate, and damage tissues in vivo. 

In March 2023, Moderna and Generation Bio formed a strategic collaboration to develop non-viral genetic medicines, granting Moderna options to license Generation Bio’s ctLNP delivery and ceDNA constructs for up to five programs 

In a recent non-human primate study, a 0.5 mg/kg dose of the company’s ctLNP-siRNA knocked down a T-cell reporter protein for about three weeks. The team plans to name an initial target and indications in mid-2025 and is preparing for a first IND in the second half of 2026.

Founded in 2016, the company raised a $110 million Series C in 2020 led by T. Rowe Price.  

DiNAQOR 

Swiss-headquartered DiNAQOR’s standout rare-disease application is inherited cardiomyopathies, where its loco-regional perfusion delivers genetic therapies directly to the heart while engineered-heart-tissue screens guide dose and target choices on human-relevant models. 

DiNAQOR operates as a multi-part group—its heart-isolated loco-regional perfusion (LRP) delivery platform, the DiNABIOS engineered-heart-tissue screening arm, and DiNAMIQS—while the core team pushes LRP toward clinical use and sources new cardiac gene-therapy programs and partners. Adjacent units include DAiNA, which builds an AI-driven precision-oncology engine that integrates genomics, proteomics, and spatial pathology to adapt care in real time; and DiNATEQ, which develops targeted drug-delivery systems, including LRP devices, to deliver therapy directly to organs with lower systemic exposure and support repeat dosing.

In 2023, Siegfried acquired 95% of DINAMIQS, making it a majority-owned subsidiary while DiNAQOR retained a minority stake and strategic partnership. In September 2025, DINAMIQS inaugurated a new cGMP viral-vector manufacturing facility in Switzerland with end-to-end capabilities from vector design through sterile filling and sealing (fill-finish).

The current lead therapy DINA-001 for hypertrophic cardiomyopathy is in Phase 1, with additional cardiomyopathy programs in discovery or preclinical, and renal programs for autosomal dominant polycystic kidney disease and glomerular diseases also in discovery to preclinical.

Taysha Gene Therapies

Taysha Gene Therapies was founded in January 2020 in Dallas, and it has a goal for direct delivery of gene therapy into spinal fluid for diseases of the central nervous system (CNS) caused by the mutation of a single gene, known as a monogenic disease treatment. 

Taysha’s approach is to fix single-gene brain disorders at the source using well-tested tools. They package a healthy gene into an adeno-associated virus AAV9, an engineered, non-disease-causing viral vector used to carry therapeutic genes into cells with a long clinical track record in the nervous system. Then, they place it directly into the cerebrospinal fluid via an outpatient intrathecal procedure so more of the therapy reaches the right brain regions with a lower dose than an IV. Inside cells, the new gene is read to make the missing or corrected protein. 

The company runs a scalable HEK293 manufacturing process—a well-characterized human embryonic kidney cell line commonly adapted to suspension culture and used for scalable AAV manufacturing via triple transfection—so each program can move from lab to clinic on the same playbook, reducing development risk and time.

Taysha’s gene therapy pipeline is led by TSHA-102 for Rett syndrome, a rare neurodevelopmental disorder caused by MECP2 mutations that primarily affects girls and leads to loss of skills, motor and breathing problems, seizures, and shortened life expectancy. TSHA-102 holds multiple U.S., EU, and other rare-disease designations and is slated to start the REVEAL pivotal trial in Q4 2025. Recent part A updates show a 100% response rate across all 12 treated patients on the pivotal primary endpoint.  

Tessera Therapeutics

Despite numerous breakthroughs in the areas of gene editing, there are still limitations of existing CRISPR-Cas technology which is mainly targeting single point-mutations and failing for longer sequences. Tessera’s innovative approach to gene-editing relies on using DNA transposases that would enable cutting and pasting the entire genes. 

Tessera Therapeutics develops Gene Writing, a genome-engineering platform that “writes” therapeutic instructions directly into DNA to address diseases at their source. Unlike tools limited to tiny edits, Gene Writing is designed to make both small and large, permanent changes to the genome, expanding what genetic medicine can reach. The company pairs this with tissue-targeted, non-viral delivery so edits happen where they’re needed, aiming to turn difficult, high-need conditions into candidates for durable, potentially curative therapies.

Tessera has recently moved its in-vivo Gene Writing programs into primate studies for inherited liver diseases where faulty genes cause protein problems and sickle cell disease. 

From its start in 2018, Tessera has raised a total of $610M over 3 funding rounds, with the latest $300M Series C in April 2022.

Ensoma

Boston-based Ensoma aims to fix blood and immune diseases by editing the body’s own master blood stem cells (HSCs) with a one-time, off-the-shelf treatment. Instead of removing cells and engineering them in a lab, it sends gene-editing instructions directly into HSCs using virus-like particles that carry larger payloads, deliver to the nucleus, and are built for scalable, GMP manufacturing. Because HSCs renew for life and make all blood and immune cell types, a precise edit or gene insert can create a durable supply of healthy cells throughout the body. The toolkit covers small fixes and large gene additions and includes editors that don’t cut DNA, allowing multiple, cell-type-tuned changes at once.

In November 2024, Ensoma revealed three in vivo HSC-engineering programs for X-linked chronic granulomatous disease (CGD), sickle cell disease, and solid tumors. Earlier this year, the FDA cleared the IND for EN-374, the first in vivo HSC-directed gene insertion therapy for X-linked CGD, enabling a Phase 1/2 trial to start in Q4 2025 with adult dose escalation followed by pediatric expansion.

Founded in 2019, Ensoma recently closed a $53M financing led by Gilead, 5AM, F-Prime, the Gates Foundation, QIA, RTW, and Viking—to fund EN-374’s Phase 1/2 enrollment and readouts and continue platform expansion in immuno-oncology and sickle cell disease. 

Prime Medicine

Cambridge-based Prime Medicine develops therapies with Prime Editing, a “search and replace” method for DNA that aims to fix mutations at their natural location without cutting both DNA strands. A related insertion method called PASSIGE is used ex vivo for T cells and in vivo with a “universal” liver-targeted LNP for genetic liver diseases. Originating from David Liu’s lab, the platform pairs a programmable guide with an enzyme that writes the correct sequence, enabling precise, predictable edits across many cell types. 

Prime Medicine’s active pipeline spans in-vivo programs for two major liver diseases, Wilson’s disease and alpha-1 antitrypsin deficiency, plus a cystic fibrosis effort backed by additional Cystic Fibrosis Foundation funding, and an ex-vivo T-cell therapy collaboration with Bristol Myers Squibb.

Recently, Prime Medicine reported the first human data for Prime Editing: a single infusion of its edited stem-cell therapy (PM359) for chronic granulomatous disease (CGD) rapidly restored the key infection-fighting signal in neutrophils—the immune system’s first responders—with no PM359-related serious side effects.

Founded in 2019, Prime Medicine closed a $144.2M follow-on equity offering in August 2025 to fund their pipeline.

Beam Therapeutics

Founded by gene-editing pioneers in 2017 and running manufacturing in North Carolina, Beam’s aim is durable, precision therapies that match each disease’s biology without double-stranded DNA breaks. 

Beam Therapeutics also develops medicines that “rewrite” DNA one letter at a time. Instead of cutting the genome, its base editors correct a harmful mutation, swap in a protective variant, dial genes up or down by tweaking control elements, or even make several precise changes at once. The company pairs this with delivery methods using electroporation for ex vivo editing of blood and immune cells, and nonviral lipid nanoparticles for in vivo delivery to the liver first, with a screening platform to find LNPs that reach other organs. 

Beam’s pipeline spans ex vivo and in vivo base editing. For sickle cell disease, BEAM-101 is an ex vivo therapy that edits a patient’s blood stem cells to switch on fetal hemoglobin, with a parallel effort to develop in vivo HSC editing via LNPs to avoid transplantation. In liver targets, BEAM-302 delivers editors by LNP to correct the PiZ variant in alpha-1 antitrypsin deficiency, and BEAM-301 uses the same liver-directed approach to fix the R83C mutation in glycogen storage disease type 1a. An in-house program, ESCAPE, also explores less toxic conditioning to help edited cells take hold.

Beam’s EHA 2025 update showed BEAM-101 delivering benefits in sickle cell disease, with enrollment in its Phase 1/2 trial now complete. BEAM-302 opened sites in the U.K., New Zealand, Australia, and the Netherlands, with initial Phase 1/2 data slated for the first half of 2025. BEAM-301 activated its first Phase 1/2 site, with patient dosing starting in early 2025. For ESCAPE conditioning, IND-enabling studies are underway and a healthy-volunteer study of BEAM-103 is planned by year-end 2025.

Topic: Biotech Ventures