TY - JOUR T1 - Split <em>Staphylococcus aureus</em> prime editor for AAV delivery JF - bioRxiv DO - 10.1101/2021.01.11.426237 SP - 2021.01.11.426237 AU - Eric J. Aird AU - Alina C. Zdechlik AU - Brian L. Ruis AU - Colette B. Rogers AU - Andrew L. Lemmex AU - Andrew T. Nelson AU - Eric A. Hendrickson AU - Daniel Schmidt AU - Wendy R. Gordon Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/01/11/2021.01.11.426237.abstract N2 - Prime editing brings immense promise to correct a large number of human pathogenic mutations and enact diverse edit types without introducing widespread undesired editing events. Delivery of prime editors in vivo would enable such edits to be introduced in a clinical setting. The coding sequence for prime editor, however, is too large to fit within the size-constrained adeno-associated virus (AAV) genome. Herein, we describe a split Staphylococcus aureus prime editor capable of being delivered by dual AAVs. We characterize the editing ability of plasmid-based versions of an S. aureus prime editor in vitro at a variety of loci with diverse edit types. We investigate various split prime editor architectures and alternative dimerization domains. Finally, we demonstrate the capacity of prime editor to be co-delivered by dual AAVs in vitro. While editing rates are lower than desired, this approach presents an important step to translate prime editing for in vivo delivery.Competing Interest StatementThe authors have declared no competing interest. ER -