Liu and colleagues developed a robust in cellulo plasmid DNA replication system in human cells for replicating plasmid-borne adeno-associated virus (AAV) Rep/Cap genes during recombinant AAV (rAAV) production. This new approach not only enables a 10- to 20-fold plasmid reduction to significantly lower manufacturing costs but also substantially enhances rAAV potency, titer, and purity.

This study developed a multi-layer inducible RNA switch that achieves transient expression of gene-delivery vectors in hepatic and non-hepatic tissues. As an exemplary application, this RNA switch triggers pulsive expression of gene editors that reduces the off-target effects and immunotoxicity of gene editing.

In the infection courses of different SARS-CoV-2 variants, disease outcomes and signatures were delineated by physiological changes, viral load, pathology, and pulmonary transcriptome analysis. This multi-dimensional landscape of disease outcomes and underlying mechanisms might provide important clues for immunotherapy of SARS-CoV-2 infection and pneumonia caused by other respiratory viruses.