Exosomes are small, single-membrane, secreted vesicles (40 nm to 100 nm) released from cells upon the fusion of a multivesicular body (MVB) containing intraluminal vesicles with the plasma membrane. Exosomes contain many membrane-associated protein complexes. Exosomes contain RNA and can transfer these extracellular RNAs (exRNAs) in functional form to other cells and tissues.
Exosomes are becoming an important tool and widely used for drug delivery nowadays. They can deliver therapies into cells that can hardly reach by other methods. siRNAs can be transfected into exosomes for delivery to target the cells and tissues. The key advantage is that surface expression of CD47 and other endogenous signaling ligands on exosomes can increase half-life by inhibiting MPS clearance and improving cellular internalization.
Exosomes have successfully delivered anti-KRAS siRNA against pancreatic cancers in mice, significantly increasing survival. Exosomes can cause a less toxic immune response in humans. However, exosomes face big challenges in scale-up production and particle heterogeneity. Codiak Biosciences is now undertaking preclinical study of exosome-loaded siRNAs for autoimmune targets and immune-oncology in macrophages.