Acuitas Therapeutics Showcases In Vivo CAR T Engineering and Lipid Innovations at ASGCT 2026
Acuitas Therapeutics concluded a prominent showing at the American Society of Gene & Cell Therapy 2026 Annual Meeting with the presentation of new research focused on advancing lipid nanoparticle (LNP) delivery systems for genetic medicines. During the conference, the company highlighted multiple scientific developments spanning targeted in vivo CAR T-cell therapy, RNA-LNP product stability, and immune system interactions associated with mRNA therapies.
The presentations reinforced Acuitas’ growing role in the gene and cell therapy landscape, particularly in the development of delivery technologies that enable more precise, effective, and potentially re-dosable nucleic acid therapeutics. The company’s research showcased efforts to improve targeting beyond the liver, increase product quality and stability, and better understand immune responses linked to LNP-based medicines.
Acuitas is widely recognized for its work in lipid nanoparticle delivery systems, which gained significant industry visibility during the rapid expansion of mRNA therapeutics and vaccines. At ASGCT 2026, the company presented new data illustrating how its latest LNP technologies may support the next generation of genetic medicines across oncology, immunology, and rare disease applications.
According to Ying Tam, the company’s scientific strategy focuses on developing highly specific and repeatable delivery approaches capable of expanding the therapeutic potential of RNA-based medicines.
“The research presented by Acuitas at ASGCT 2026 showcases our holistic approach to pave the way for highly specific and re-dosable genetic medicines,” Tam stated. He added that the company’s findings related to in vivo CAR T-cell engineering and RNA-lipid adduct mechanisms contribute to raising industry standards in LNP delivery technologies. Tam also noted that several Acuitas partners presented promising therapeutic data during the conference using Acuitas’ LNP systems in their own clinical programs.
One of the central highlights of Acuitas’ presentations involved the development of a targeted extended circulation lipid nanoparticle platform designed to engineer CAR T cells directly within the body. Traditionally, CAR T-cell therapies require a complex ex vivo manufacturing process in which patient immune cells are collected, genetically modified in a laboratory, and reinfused into the patient. Acuitas’ approach aims to simplify this process through direct in vivo delivery of CAR-encoding messenger RNA to immune cells.
The company developed a novel extended circulation LNP, referred to as ecLNP, capable of selectively delivering CAR-encoding mRNA to CD8-positive T cells. This work was conducted in collaboration with Athebio, which contributed its proprietary Athebody® designed ankyrin repeat proteins, commonly known as DARPins. These engineered binding proteins are designed to enable highly specific cell targeting.
According to the data presented, the ecLNP composition substantially improved circulation time in murine models, extending plasma half-life from approximately 15 minutes to nearly two hours. Researchers also reported that the incorporation of DARPins into the LNP system reduced liver expression by approximately tenfold compared to standard lipid nanoparticle formulations. This reduction in liver targeting is particularly important because many conventional LNP systems naturally accumulate in hepatic tissues, limiting their ability to effectively target other organs or cell types.
In nonhuman primate studies, Acuitas demonstrated that administration of ecLNPs encapsulating CD20 CAR mRNA produced CAR expression in more than 60% of circulating CD8-positive T cells. The engineered CAR T cells subsequently induced complete and sustained depletion of B cells in peripheral blood as well as in bone marrow, spleen, and lymph node tissues at doses as low as 0.25 milligrams per kilogram.
The findings suggest that targeted LNP systems may offer a pathway toward scalable and less invasive CAR T-cell therapies. If validated in future clinical studies, this strategy could potentially simplify manufacturing logistics, reduce treatment costs, and broaden patient access to engineered cell therapies.
In addition to advancements in targeting technology, Acuitas also presented new findings related to the chemical stability and quality control of mRNA-LNP products. Specifically, the company focused on the issue of RNA-lipid adduct formation, a phenomenon that can negatively impact therapeutic performance and long-term stability.
RNA-lipid adducts are undesired chemical bonds formed between ionizable lipid impurities and messenger RNA molecules. These interactions can inhibit mRNA translation and reduce protein expression levels, potentially compromising the efficacy of LNP-delivered therapeutics. Acuitas noted that such impurities are often difficult to detect using traditional mRNA purity assays, making them an important but underrecognized challenge in the manufacturing of RNA medicines.
Chris Barbosa explained that understanding the chemical mechanisms responsible for RNA-lipid adduct formation is essential for improving product consistency and potency.
“RNA-lipid adduct formation is an important issue affecting LNP-delivered therapies,” Barbosa said. He explained that Acuitas’ research enables the company to better control critical impurities and establish manufacturing quality targets for approved lipid suppliers, ensuring that partners receive delivery systems with high integrity and clinical-grade performance.
The company identified aldehydes, generated either as process impurities or degradation byproducts of ionizable lipids, as the primary drivers of RNA-lipid adduct formation. To detect and quantify these impurities, Acuitas developed advanced analytical techniques including ion-pairing reversed-phase chromatography and liquid chromatography-mass spectrometry.
Researchers also demonstrated a direct relationship between increased lipid adduct formation and reduced protein expression in murine models. Higher adduct levels were associated with lower serum IgG expression, indicating a measurable decline in therapeutic activity. However, the studies showed that elevated aldehyde impurities and lipid adduct levels did not appear to negatively impact liver tolerability in animal models.
Acuitas further reported that adduct formation is strongly influenced by storage time, temperature conditions, and the impurity profile of specific ionizable lipid batches. As a result, the company emphasized the importance of comprehensive raw material screening to ensure consistent quality in final LNP drug products.
Beyond delivery efficiency and product stability, Acuitas also shared research exploring interactions between lipid nanoparticles and the immune system, an area of growing importance as repeated dosing strategies become more common in RNA therapeutics.
One presentation focused on infusion-related reactions associated with LNP-based medicines. To better investigate these responses, Acuitas developed an optimized human whole blood assay designed to evaluate immune stimulation caused by both LNPs and mRNA payloads. The assay also aimed to identify therapeutic agents capable of mitigating inflammatory responses without relying heavily on steroids.
The company reported that clinically relevant compounds such as baricitinib, a JAK1/2 inhibitor, and pegcetacoplan, a complement inhibitor, effectively reduced immune stimulation in donors exhibiting high inflammatory responses. Researchers suggested that such targeted mitigation strategies could support repeated dosing of mRNA-LNP therapies while minimizing the long-term side effects associated with chronic steroid use.
Acuitas also presented findings related to variability observed in nonhuman primate studies involving mRNA-LNP therapies. Researchers analyzed liver transcriptome profiles from 20 nonhuman primates following intravenous administration of human IgG mRNA-LNP formulations.
Although treatment responses demonstrated an 18-fold variation in potency between animals, the variability did not correlate with body weight, liver enzyme elevations, or pharmacokinetic differences. Instead, the analysis identified differential activation of immune-related genes including FOSL1, CCL18, and DHRS9, suggesting that individual immune modulation pathways may significantly influence pharmacodynamic responses to mRNA-LNP therapies.
These findings underscore the complexity of biological responses to genetic medicines and highlight the need for deeper mechanistic understanding as the field advances toward broader clinical applications.
Overall, Acuitas’ presentations at ASGCT 2026 highlighted the company’s continued investment in addressing some of the most important scientific and manufacturing challenges facing RNA therapeutics and gene delivery technologies. From targeted in vivo CAR T-cell generation to improvements in product stability and immune modulation, the research reflects a comprehensive effort to advance the safety, precision, and scalability of next-generation genetic medicines.
As the gene and cell therapy industry continues to evolve rapidly, Acuitas appears positioned as a key technology provider supporting developers seeking more effective delivery systems for RNA-based therapeutics. The company’s latest findings may contribute to future innovations across oncology, immunology, and regenerative medicine, particularly as demand grows for therapies capable of safe, repeatable, and tissue-specific genetic delivery.
About Acuitas Therapeutics
Acuitas Therapeutics Inc., the global leader in lipid nanoparticle (LNP) delivery systems for nucleic acid therapeutics, is a Vancouver-based company collaborating with pharmaceutical and biotech companies, academic researchers, and global health organizations to advance a broad range of medicines for a variety of diseases.
Acuitas’ clinically validated LNP technology has had a profound global impact — most notably enabling the Pfizer-BioNTech COVID-19 vaccine, COMIRNATY®, which has protected billions of people in more than 180 countries. Its technology also enables ONPATTRO® by Alnylam Pharmaceuticals, the first FDA-approved RNAi therapeutic for treating the rare and fatal disease transthyretin amyloidosis. More recently, Acuitas’ LNP technology has delivered other groundbreaking firsts: the first in-human proof of concept for genome base editing and the first personalized CRISPR therapy.
Today, Acuitas is advancing next-generation LNP to support a variety of therapeutic modalities. This includes targeted LNP for extrahepatic therapies such as in vivo CAR T-cells, gene editing therapies across multiple DNA editing technologies, epigenetic medicines to modulate gene expression without altering DNA, and multivalent vaccines for infectious diseases — such as malaria, HIV/AIDS, and tuberculosis — as well as oncology vaccines, including personalized cancer vaccines.
