The efficient delivery of proteins into cells is needed to fully realize the potential of protein-based therapeutics. Current protein delivery strategies generally suffer from poor endosomal escape and low tolerance for serum. Here, the genetic fusion of a supercharged polypeptide, called SCP, to a protein provides a generic method for intracellular protein delivery. It allows efficient protein endocytosis and endosomal escape and is capable of potently delivering various proteins with a range of charges, sizes, and bioactivities into the nucleus of living cells. SCP is discovered to bind directly to the nuclear import protein importin β1 and gains access to the nucleus. Furthermore, SCP shows minimal hemolytic activity and stability in serum and lacks toxicity and immunogenicity in vivo. Effective gene editing can be achieved by SCP-mediated delivery of Cas9 protein and guide RNA. This study may provide an efficient and useful tool for the design and development of cell-nucleartargeted drug delivery.

A variety of opinions exist on the potential of probiotics to provide relief from chronic constipation with much focus placed on their mechanism of action and causes of heterogeneity in...

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Bipolar resistance switching behaviors in the M/La0.7Ca0.3MnO3/Pt (M=Pt, Ag, Cu, Al, Ti, and W) junctions were investigated. We found that the switching polarities of the junctions for M=Pt, Ag, and Cu were opposite to those for M=Al, Ti, and W. This phenomenon was attributed to the different Gibbs free energy of the metal oxide formation. Based on Auger electron spectroscopy measurement of the M/La0.7Ca0.3MnO3 interfaces, the switching mechanisms were further discussed in terms of metal electrode redox reaction for M=Al, Ti, and W and oxygen vacancy generation/annihilation in the La0.7Ca0.3MnO3 film for M=Pt, Ag, and Cu, respectively.