biostudies-literatureWhitley JANEI NIH HHSNIAID NIH HHSNCI NIH HHSe12196https://www.ebi.ac.uk/biostudies/studies/S-EPMC8982324biostudies-literatureUnknown11(4)CRISPR/Cas9 genome editing is a very promising avenue for the treatment of a variety of genetic diseases. However, it is still very challenging to encapsulate CRISPR/Cas9 machinery for delivery. Protein N-myristoylation is an irreversible co/post-translational modification that results in the covalent attachment of the myristoyl-group to the N-terminus of a target protein. It serves as an anchor for a protein to associate with the cell membrane and determines its intracellular trafficking and activity. Extracellular vesicles (EVs) are secreted vesicles that mediate cell-cell communication. In this study, we demonstrate that myristoylated proteins were preferentially encapsulated into EVs. The octapeptide derived from the leading sequence of the N-terminus of Src kinase was a favourable subJournal of extracellular vesiclesEncapsulating Cas9 into extracellular vesicles by protein myristoylation.PMC8982324R21 EY028671R01 EY031748P30 EY005722R21 AI171944R21 AI157831U01 CA225784Desrochers EGXie ZRYe CAlsaidan OASulejmani ECai JCai HKim SWhitley JALiu YBeharry ZKlingeborn MRickman CBLou LfalseEncapsulating Cas9 into extracellular vesicles by protein myristoylation.CRISPR/Cas9 genome editing is a very promising avenue for the treatment of a variety of genetic diseases. However, it is still very challenging to encapsulate CRISPR/Cas9 machinery for delivery. Protein N-myristoylation is an irreversible co/post-translational modification that results in the covalent attachment of the myristoyl-group to the N-terminus of a target protein. It serves as an anchor for a protein to associate with the cell membrane and determines its intracellular trafficking and activity. Extracellular vesicles (EVs) are secreted vesicles that mediate cell-cell communication. In this study, we demonstrate that myristoylated proteins were preferentially encapsulated into EVs. The octapeptide derived from the leading sequence of the N-terminus of Src kinase was a favourable sub2022-01-01T00:00:00Z2022 Apr2026-05-09T19:22:27.12Z2025-04-06T03:58:39.81ZS-EPMC89823243538435210.1002/jev2.12196