Abstract: Engineered Type II Cas polypeptides with reduced immunogenicity, CRISPR-Cas systems thereof, compositions thereof, delivery systems thereof, and methods of use thereof for modifying target polynucleotides, such as, for example, in cells.

Abstract: Provided herein are compositions, systems, and methods for delivering cargo to a target cell. The compositions, systems, and methods comprise one or more polynucleotides encoding one or more LTR retroelement polypeptides for forming a delivery vesicle and one or more capture moieties for packaging a cargo within the delivery vesicle. The one or more LTR retroelement polypeptides for forming a delivery vesicle may comprise two or more of an LTR retroelement gag protein, a retroelement envelope protein, an LTR retroelement reverse transcriptase, or a combination thereof. The LTR retroelement polypeptide alone, the LTR retroelement envelope protein alone, or both the LTR retroelement-derived polypeptide and LTR retroelement envelope protein may be endogenous. In some embodiments the LTR-retroelement-derived polypeptide is a PNMA polypeptide.

Abstract: Described in certain example embodiments herein are engineered delivery vesicle generations systems capable of producing engineered delivery vesicles containing two or more different retroelement polypeptides. Also described herein are methods of making and using the engineered delivery vesicles, such as to deliver one or more cargoes.

Abstract: Described herein are engineered paraneoplastic Ma protein (PNMA) capable of forming a capsid. In some embodiments, the engineered PNMA proteins comprise one or more modifications that enhance binding or loading of a cargo into the capsid, one or more modifications that modify cell-specificity of the capsid, one or more modifications that enhance intracellular delivery of the capsid, or a combination thereof. Also described herein are delivery systems comprising capsids comprising an engineered PNMA protein and a cargo.