CRISPR gene editing shows Phase 3 success in hereditary angioedema

Intellia Therapeutics has reported positive Phase 3 results for its in vivo CRISPR gene editing therapy lonvoguran ziclumeran (lonvo-z), marking a potential milestone for one-time genetic treatments. In the global HAELO trial, a single dose reduced hereditary angioedema (HAE) attacks by 87 percent compared to placebo, with most patients remaining attack-free and off chronic therapy during the six-month evaluation period.

The therapy works by inactivating the KLKB1 gene to durably suppress kallikrein and bradykinin production, addressing the root cause of the disease. Among treated patients, 62 percent experienced complete freedom from both attacks and ongoing medication, while safety findings were favorable, with only mild-to-moderate adverse events reported.

Intellia has initiated a rolling biologics license application with the FDA and is targeting a potential US launch in 2027. If approved, lonvo-z could become the first in vivo CRISPR-based therapy to reach the market. Source

Flagship launches Serif to develop programmable DNA medicines

Flagship Pioneering has unveiled Serif Biomedicines, a new startup focused on establishing “modified DNA” as a therapeutic platform that combines features of mRNA and gene therapy. Backed by an initial $50 million investment, the company aims to create programmable, durable, and redosable medicines by overcoming longstanding challenges associated with DNA delivery and immunogenicity.

Serif’s approach involves chemically and structurally engineered DNA, paired with mRNA co-factors and lipid nanoparticle delivery systems, to enable sustained gene expression without integrating into the genome. The platform is designed to support repeat dosing – an advantage over traditional gene therapies – while offering longer-lasting effects than RNA-based approaches. 

Preclinical data to be presented suggest the technology is well tolerated in non-human primates and can drive durable gene expression with therapeutic effects following intravenous administration. The company will initially target rare diseases and immune-related conditions, positioning modified DNA as a potential new modality in the growing field of programmable medicines. Source 

Cabaletta partners with Cellares to scale CAR-T manufacturing for autoimmune diseases

Cabaletta Bio has signed a 10-year commercial supply agreement with Cellares to industrialize production of its CD19-targeting CAR-T therapy, rese-cel, as it advances toward potential regulatory approval. The deal aims to enable large-scale, automated manufacturing capable of producing thousands of patient-specific batches per year at significantly reduced cost.

The partnership will leverage Cellares’ Cell Shuttle and Cell Q platforms, which automate end-to-end manufacturing and quality control. The companies say this approach could lower labor requirements, improve scheduling flexibility, and support global expansion, addressing a key bottleneck in bringing CAR-T therapies beyond oncology and into more prevalent autoimmune diseases.

Rese-cel is currently being evaluated across multiple indications, including myositis, lupus, and systemic sclerosis, with a planned biologics license application in myositis next year. Initial translational data from Cellares-manufactured batches are expected in 2026. Source

AI-designed recombinases target next frontier in gene editing

Profluent has announced a strategic collaboration with Eli Lilly to develop AI-designed recombinases capable of enabling large-scale, precise DNA editing. The partnership aims to address a key limitation in genetic medicine: the ability to insert long stretches of DNA – or entire genes – at specific genomic locations.

Unlike conventional approaches that rely on naturally occurring enzymes, Profluent is using generative AI to design custom recombinases tailored to exact DNA targets. The companies hope this approach will unlock therapies for diseases driven by diverse mutations, where current gene editing tools fall short.

Under the deal, Lilly will take selected candidates through in vivo research and clinical development, while Profluent is eligible for up to $2.25 billion in milestone payments. Source

Orca-Q receives RMAT designation for high-risk blood cancers

Orca Bio has received FDA Regenerative Medicine Advanced Therapy (RMAT) designation for Orca-Q, its second-generation investigational allogeneic T-cell immunotherapy for high-risk hematologic malignancies. The designation is based on preliminary Phase 1 data showing encouraging outcomes across overall survival, acute and chronic graft-versus-host disease, and non-relapse mortality.

Orca-Q combines donor-derived stem cells with selected T-cell subsets, manufactured using Orca Bio’s high-precision platform. The therapy is being evaluated across multiple patient groups, including those with haploidentical or mismatched donors and those receiving reduced-intensity or non-myeloablative conditioning. The ongoing Phase 1 trial has recently been expanded to include additional cohorts, with new clinical findings and longer follow-up data expected in 2026. Source

Senescent immune cells linked to CAR-T therapy failure

Researchers at Rutgers University have identified a potential reason why CAR-T cell therapy fails in some patients: the poor quality of the starting immune cells. The study shows that many patients’ CD8+ T cells are in a senescent (aged and dysfunctional) state before engineering, limiting their ability to expand, migrate, and kill cancer cells effectively.

By analyzing both donor cells and retrospective clinical data from lymphoma patients, the team found that strong “senescence signatures” in the starting material and final CAR-T product were linked to significantly lower response rates. Importantly, the researchers showed that this effect is driven by cellular senescence itself rather than chronological age, with the underlying genetic program already present early in life.

The team also identified key transcription factors controlling this senescence program and demonstrated that modulating them can partially restore more functional gene expression patterns. The findings suggest that pre-treatment profiling of T-cell senescence could help predict CAR-T outcomes and guide patient selection, while also pointing to new strategies for improving cell therapy performance. Source

Natural compound enhances CAR-T potency and tackles tumor resistance

A screen of more than 3,000 compounds has identified a natural molecule that can boost CAR-T performance by targeting immunosuppressive cells. The team from China found that TAIII blocks the adenosine A2A receptor, a key immune checkpoint involved in suppressive signaling. In vitro and in lymphoma models, the compound restored CAR-T function, improved tumor killing, reduced relapse, and extended survival. It also enhanced the performance of patient-derived CAR-T cells.

In solid tumor models, TAIII helped “turn cold tumors hot” by reducing immunosuppressive cells and increasing cytotoxic T-cell activity, while showing synergy with both CAR-T and anti-PD-1 therapies. Notably, the compound achieved effects comparable to clinical-stage A2A inhibitors at lower doses. Source

Eating boosts T-cell performance with implications for immunotherapy timing

Eating induces a temporary metabolic state that enhances T-cell function, with effects that can persist for days, according to researchers at the University of Pittsburgh. The study found that T cells collected after a meal display improved metabolic readiness and respond more robustly upon activation compared to those collected during fasting.

In both human and mouse experiments, the post-meal advantage was linked to circulating dietary fats, which T cells can directly uptake and use to fuel immune responses. This metabolic boost increased protein production rather than altering gene expression, and some T cells retained enhanced functionality for up to a week after exposure to this nutrient-rich state.

The findings also extend to CAR-T therapy. When researchers generated CAR-T cells from post-meal T cells, the engineered cells showed better persistence and tumor control in preclinical models than those derived from fasted cells. The work highlights metabolic timing as a previously overlooked variable in immunology and cell therapy workflows, suggesting that when immune cells are collected could influence therapeutic outcomes. Source

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