Summary of modifications used to increase therapeutic efficacy of EV-based therapeutics. (1) Incorporation of various targeting moieties (nanobodies, bispecific antibodies, peptides) to target specific antigens on target cells or glycan groups/ligands that can bind to receptors on target cells. (2) Addition of CD47, PEG or removal of sialic acid to reduce clearance by macrophages of the RES. (3) Encapsulation of nucleic acids (plasmid DNA, mRNA, miRNA, siRNA), therapeutic proteins and small molecule drugs which are then delivered to target cells to carry out their therapeutic effects. Figure was created with Biorender.