Exosomal loading using hydrophobically modified oligonucleotides

A method of loading exosomes with a therapeutically effective amount of an oligonucleotide cargo, said method comprising:

• providing oligonucleotides comprising one or more hydrophobic modifications at a concentration of 1.25 μM to 20 μM, wherein the one or more hydrophobic modifications comprise a hydrophobic moiety conjugated to the oligonucleotide;
• wherein the hydrophobic moiety is selected from the group consisting of a sterol, GM1, a lipid, a vitamin, a small molecule, a peptide, or a combination thereof;
• and
• incubating the oligonucleotides comprising one or more hydrophobic modifications with a population of exosomes, wherein the method takes place in the absence of ultracentrifugation, electroporation and a separately added transfection reagent;
• thereby loading the exosomes with a therapeutically effective amount of an oligonucleotide cargo;
• wherein the therapeutically effective amount is an average of 1000-3000 oligonucleotide molecules per exosome.