mRNA-LNPs induce immune activation and cytokine release in human whole blood assays across diverse health conditions.

RNA medicines have become a promising platform for therapeutic use in recent years. Understanding the immunomodulatory effects of novel mRNA-lipid nanoparticles (LNPs) is crucial for future therapeutic development. An in vitro whole blood assay was developed to assess the impact of mRNA-LNPs on immune cell function, cytokine release, and complement activation.

Single cell and TCR analysis of immune cells from AAV gene therapy-dosed Duchenne muscular dystrophy patients.

Clinical trials for Duchenne muscular dystrophy (DMD) are assessing the therapeutic efficacy of systemically delivered adeno-associated virus (AAV) carrying a modified transgene. High vector doses (>1E14 vg/kg) are needed to globally transduce skeletal muscles; however, such doses trigger immune-related adverse events. Mitigating these immune responses is crucial for widespread application of AAV-based therapies.

Comparison and cross-validation of long-read and short-read target-enrichment sequencing methods to assess AAV vector integration into host genome.

Evaluation of host integration profiles by adeno-associated virus (AAV) is an important component of de-risking novel AAV gene therapies. Targeted enrichment sequencing (TES) is a cost-effective and comprehensive method for assessing integration. Most published TES datasets have been generated using short-read sequencing, which enables quantitation of integration sites (ISs) and identifies patterns such as hotspots or clonal expansion.