Abstract: The disclosure provides compositions and methods for modifying a target nucleic acid. In some embodiments, a composition can include a lipid nanoparticle including a targetable nuclease or an mRNA encoding a targetable nuclease, a DNA-binding protein or an mRNA encoding a DNA-binding protein, and a donor template comprising a homology directed repair (HDR) template and one or more DNA-binding protein target sequences. In some embodiments, a composition can include a Cas protein, one or more single guide RNAs (sgRNAs), and a lipid nanoparticle.