Delivery of Prime editing in human stem cells using pseudoviral NanoScribes particles

    The Paper of the Day article describes the development of a virus-like particle (VLP) system called "Nanoscribes" that can efficiently deliver prime editing components into a variety of human cells, including cell lines, primary myoblasts, induced pluripotent stem cells (iPSCs), and iPSC-derived hematopoietic stem cells (HSCs). The key features of the Nanoscribes system include: - Optimization of the prime editor construct by adding nuclear export signals, protease cleavage sites, and deleting the RNase H domain to improve editing efficiency.- Incorporation of stabilizing RNA structures like the TAR stem-loop into the prime editing guide RNA (pegRNA) to further enhance editing.- Use of a Pol II promoter system to express the pegRNA, which allows for more flexible design compared to Pol III promoters.- Packaging of the prime editing components into VLPs using a Gag-based system, which enables efficient delivery into target cells.