%0 Journal Article %J Cell %D 2022 %T Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins %A Banskota, Samagya %A Raguram, Aditya %A Suh, Susie %A Du, Samuel W %A Davis, Jessie R %A Choi, Elliot H %A Wang, Xiao %A Nielsen, Sarah C %A Newby, Gregory A %A Randolph, Peyton B %A Osborn, Mark J %A Kiran Musunuru %A Palczewski, Krzysztof %A Liu, David R %X Methods to deliver gene editing agents in vivo as ribonucleoproteins could offer safety advantages over nucleic acid delivery approaches. We report the development and application of engineered DNA-free virus-like particles (eVLPs) that efficiently package and deliver base editor or Cas9 ribonucleoproteins. By engineering VLPs to overcome cargo packaging, release, and localization bottlenecks, we developed fourth-generation eVLPs that mediate efficient base editing in several primary mouse and human cell types. Using different glycoproteins in eVLPs alters their cellular tropism. Single injections of eVLPs into mice support therapeutic levels of base editing in multiple tissues, reducing serum Pcsk9 levels 78% following 63% liver editing, and partially restoring visual function in a mouse model of genetic blindness. In vitro and in vivo off-target editing from eVLPs was virtually undetected, an improvement over AAV or plasmid delivery. These results establish eVLPs as promising vehicles for therapeutic macromolecule delivery that combine key advantages of both viral and nonviral delivery. %B Cell %V 185 %P 250-265.e16 %8 2022 Jan 20 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/35021064?dopt=Abstract %R 10.1016/j.cell.2021.12.021