Calcific aortic valve disease (CAVD) is the most prevalent acquired valve heart disorder in aging populations. Its most severe form in aortic valve stenosis (AVS), with an average survival of 2-3 years once symptoms appear. The early diagnosis of AVS based on circulating biomarkers is crucial to label high-risk patients before they progress to the severe form.

Loss-of-function mutations in the CTNNB1 gene cause β-catenin deficiency, leading to CTNNB1 syndrome, a rare neurodevelopmental disorder marked by motor and cognitive impairments. Because the disease stems from single-allele mutations that vary widely, a broadly applicable corrective strategy is needed. Since CTNNB1 is dosage-sensitive, therapies must preserve normal regulation, and in some cases may also need to suppress harmful mutant transcripts.

Despite the success of traditional viral-based CAR T-cell therapies against several blood malignancies, their efficacy remains limited against solid tumors. Non-viral engineering of CAR T cells using electroporation or lipid nanoparticle delivery of CAR-encoding mRNA achieves high but transient CAR expression, highlighting the limitations of current preclinical models for evaluating mRNA-based CAR T cells.