AbstractNumerous biomolecular condensates coexist within cells, yet the factors governing their miscibility remain poorly understood. Here, by examining 28 intrinsically disordered regions in 378 pairwise combinations, we identify key sequence determinants of condensate miscibility: serine and aromatic residues promote miscibility, while charged amino acids drive immiscibility. Mutagenesis expe...

AbstractCulex quinquefasciatus is a major vector of West Nile virus and other pathogens, yet genetic population suppression tools for this species remain limited. Here, we develop a self-limiting, CRISPR-based suppression gene drive system targeting doublesex, close to the male-determining locus, promoting male transmission. A recoded dsxM sequence converts females into sterile intersexes, prev...

AbstractThe tumor glycocalyx forms a protective shield that masks checkpoint proteins and compromises the efficacy of immunotherapies. While the bacterial protease StcE can degrade this barrier by cleaving O-glycosylated mucin domains, its therapeutic potential is hindered by off-target toxicity and high immunogenicity. To overcome these limitations, we developed a biomimetic platform of cell m...

AbstractBrain PET is a powerful imaging modality that directly reflects cerebral metabolic activity, making it an essential tool for human brain research. However, conventional brain PET typically requires subjects to remain stationary in a sitting or supine position during scanning. This study evaluated the performance of SmartBrain, a wearable brain PET system for real-time imaging. Methods: ...

AbstractThe clinical success of gene therapy depends critically on the development of delivery platforms capable of achieving precise, efficient and tissue-specific delivery of genetic payloads in vivo. A diverse array of carriers, including viral, non-viral, synthetic and natural vectors, have been explored to address this challenge. Among them, adeno-associated viruses, lipid nanoparticles an...

Abstract3D single-particle tracking has the potential to resolve the molecular-level forces that dictate particle motion in biological systems. However, the information gleaned from 3D single-particle tracking often cannot resolve underlying nanoscale potentials due to limited spatiotemporal resolution. To this end, we introduce an active-feedback 3D tracking microscope that utilizes silver nan...

AbstractN-terminal cysteine presents a uniquely reactive 1,2-aminothiol motif that enables site-specific modification of peptides and proteins composed solely of canonical amino acids. For both in vitro and in vivo applications, this operationally simple chemistry is an attractive alternative to bioorthogonal strategies that require noncanonical handles. However, most 1,2-aminothiol-selective r...