Zhai, H.; Liu, Y.; Beechey-Newman, O.; Modis, Y.

Retroelements and endogenous viruses make up more than a third of most genomes. Long viewed as purely parasitic, it is now clear retroelements can be repurposed to fulfill vital functions, but the properties of retroelement-derived proteins remain largely uncharted. Here, we identify the Atlas viruses, a new family of endogenous viruses in nematodes. Atlas viruses are distinguished by their divergent retrovirus-like genomes, phlebovirus-like glycoproteins, and spumavirus-like capsid assemblies. Cryo-EM structures of capsid proteins from different Atlas viruses reveal icosahedral particles 20 to 60-nm in diameter. Atlas particles spontaneously package RNA, are endocytosed, and disassemble at endosomal pH. They can be readily produced at scale and functionalized through structure-guided engineering. The properties of Atlas capsids make them attractive candidates as vehicles for tissue-specific delivery of RNA-based therapies, with key advantages over existing virus-based delivery systems for gene and cell therapies.