Abstract: Systems and methods for targeted gene modification, targeted insertion, perturbation of gene transcripts, and nucleic acid editing. Novel nucleic acid targeting systems comprise components of CRISPR systems and non-LTR retrotransposon elements.

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 several example embodiments herein are engineered programmable pattern recognition compositions and uses thereof. In an embodiment, the engineered protein contains an NTPase of a Signal Transduction ATPases with Numerous-associated Domains (STAND) superfamily (STAND NTPase), comprising a pathogen-associated molecular pattern (PAMP) recognition activity, wherein the STAND NTPase and the PAMP recognition activity are derived from the same or different prokaryotes.

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.