SOMERVILLE, Mass.– Tessera Therapeutics has shared new preclinical results showcasing the progress of its Gene Writing™ technology across multiple therapeutic areas, including alpha-1 antitrypsin deficiency (AATD), phenylketonuria (PKU), sickle cell disease (SCD), and in vivo T cell therapies. The findings were presented at the American Society of Gene and Cell Therapy’s 28th Annual Meeting in New Orleans.
The company reported compelling editing efficiency using its RNA Gene Writers in non-human primates (NHPs), achieving an estimated 76% and 70% gene editing in liver cells for AATD and PKU, respectively. These results underscore the potential of Tessera’s approach to achieve durable and precise in vivo genome modifications.
In AATD, a disease caused by mutations in the SERPINA1 gene, Tessera’s RNA Gene Writer demonstrated robust liver editing in NHPs following a single 1.5 mg/kg dose using its proprietary lipid nanoparticle (LNP) delivery system. Editing was highly specific to the liver, with no off-target effects detected in other tissues, including germline cells. Additional studies confirmed that gene correction remained stable for at least six months. Mouse models treated at lower doses also showed high levels of genomic correction and protein restoration, with significant reductions in toxic liver aggregates.
Similarly, in PKU, a disorder resulting from mutations in the PAH gene that leads to toxic phenylalanine buildup, Tessera’s RNA Gene Writer delivered 70% editing in NHP hepatocytes and normalized plasma phenylalanine levels in a humanized mouse model. These results indicate the therapy’s potential for reversing the metabolic defects associated with the condition.
In the field of hematology, Tessera presented preclinical data showing its RNA Gene Writers achieved over 20% gene correction in long-term hematopoietic stem cells (LT-HSCs) in NHPs for sickle cell disease. This level of editing approaches curative thresholds, with up to 50% of HSCs showing edits in some cases. The results were consistent across multiple species and sustained for up to six months, supporting the durability of the edits. In humanized mouse models, correction rates of 35% were achieved in cells from individuals with SCD. The findings suggest a potential non-viral, non-transplant-based therapeutic option for the disease.
Tessera also presented advancements in applying its Gene Writing and LNP platforms to in vivo T-cell therapies, aimed at treating cancer and autoimmune diseases. In preclinical mouse studies, a single infusion of RNA Gene Writer generated functional CAR-T cells targeting CD19 and CD20. These engineered cells expanded in vivo and led to complete tumor clearance in a xenograft model. In another study using a humanized mouse model, up to 30% of resting T cells were successfully edited to express CD20-directed CARs, resulting in the elimination of circulating human B cells.
“These findings highlight the broad applicability and powerful potential of our Gene Writing and delivery platforms,” said Dr. Michael Severino, CEO of Tessera Therapeutics. “The ability to achieve high-efficiency, durable gene editing in vivo—whether in liver cells, stem cells, or T cells—positions Tessera to advance a new generation of genetic medicines for serious and currently untreatable diseases.”
As Tessera moves toward clinical development, the data presented at ASGCT signal meaningful steps toward therapies that could transform treatment for monogenic and immune-related diseases through durable, precise, and scalable in vivo genome engineering.
