Clinical deployment of oligonucleotides requires delivery technologies that improve stability, target tissue accumulation and cellular internalization. Exosomes show potential as ideal delivery vehicles. However, an affordable generalizable system for efficient loading of oligonucleotides on exosomes remain lacking. Here, we identified an Exosomal Anchor DNA Aptamer (EAA) via SELEX against exosomes immobilized with our proprietary CP05 peptides. EAA shows high binding affinity to different exosomes and enables efficient loading of nucleic acid drugs on exosomes. Serum stability of thrombin inhibitor NU172 was prolonged by exosome-loading, resulting in increased blood flow after injury in vivo. Importantly, Duchenne Muscular Dystrophy PMO can be readily loaded on exosomes via EAA (EXO EAA-PMO ). EXO EAA-PMO elicited significantly greater muscle cell uptake, tissue accumulation and dystrophin expression than PMO in vitro and in vivo. Systemic administration of EXO EAA-PMO elicited therapeutic levels of dystrophin restoration and functional improvements in mdx mice. Altogether, our study demonstrates that EAA enables efficient loading of different nucleic acid drugs on exosomes, thus providing an easy and generalizable strategy for loading nucleic acid therapeutics on exosomes. Synopsis This study identifies an exosome-binding DNA aptamer (Exosomal Anchor Aptamer—EAA) and demonstrates that EAA binds to exosomes of different origins effectively and enables efficient loading of different nucleic acid drugs on exosomes. This study provides an easy generalizable strategy for loading nucleic acid therapeutics on exosomes orthogonal to CD63-binding peptides, which are better suited for protein and peptide loading. EAA showed high binding affinity to exosomes irrespective of origin. EAA enabled loading of different nucleic acid drugs on exosomes, with thrombin DNA aptamer inhibitor NU172 loaded on exosomes extended the serum stability. Duchenne Muscular Dystrophy (DMD) phosphorodiamidate morpholino oligomers (PMOs) were efficiently loaded on exosomes via EAA to form EXO EAA-PMO and systemic administration EXO EAA-PMO at low doses improved muscle function and pathologies in dystrophic mice. This study identifies an exosome-binding DNA aptamer (Exosomal Anchor Aptamer - EAA) and demonstrates that EAA binds to exosomes of different origins effectively and enables efficient loading of different nucleic acid drugs on exosomes. This study provides an easy generalizable strategy for loading nucleic acid therapeutics on exosomes orthogonal to CD63-binding peptides, which are better suited for protein and peptide loading.