Therapeutic Potential of Engineered Extracellular Vesicles

Abstract

Extracellular vesicles (EVs) comprise a heterogeneous group of small membrane vesicles, including exosomes, which play a critical role in intracellular communication and regulation of numerous physiological processes in health and disease. Naturally released from virtually all cells, these vesicles contain an array of nucleic acids, lipids and proteins which they transfer to target cells within their local milieu and systemically. They have been proposed as a means of "cell-free, cell therapy" for cancer, immune disorders, and more recently cardiovascular disease. In addition, their unique properties of stability, biocompatibility, and low immunogenicity have prompted research into their potential as therapeutic delivery agents for drugs and small molecules. In this review, we aim to provide a comprehensive overview of the current understanding of extracellular vesicle biology as well as engineering strategies in play to improve their therapeutic potential.

Milk MicroRNAs in Health and Disease

“…Therefore, the bulk of evidence supports milk EV stability, bioaccessibility, bioavailability, and biological activity and recent evidence supports their biocompatibility (that is, the lack of side effects associated with their consumption or their direct injection into the circulatory system in vivo ; Mentkowski, Snitzer, Rusnak, & Lang, ; Munagala et al., ; Somiya et al., ). Nevertheless, concerns about the biological content of EVs, and environmental context of their use, were raised and must be taken into consideration when using milk EVs as therapeutic tools (Melnik, ; Melnik & Schmitz, ; Melnik et al., ; Nordgren et al., ).…”

Identification of protein markers for extracellular vesicle (EV) subsets in cow's milk

“…This discrimination is of high importance when studying the biological activity of EVs, because it is only by ensuring reproducible isolation procedures and relative purity of EVs that one can associate a function to a specific EV subset [1,15,19,26]. It is also of importance to determine which integrins are present on the surface of these EVs, since these might lead to the accumulation of specific EV subsets in specific cell types/organs; milk EVs may thus be used as a vehicle to develop strategies based on their potential ability to deliver therapeutics to specific diseased cell types/organs [27][28][29].…”

Engineered Extracellular Vesicles as a Reliable Tool in Cancer Nanomedicine

“…A frequently applied method to modify EVs in vitro, i.e., loading cargo molecules or accomplishing membrane functionalization, is through the engineering of parent cells. Cell engineering methods, such as genetic and metabolic modification and exogenous delivery, can alter the surface expression and cargo content of newly-produced EVs and thus enhance their biocompatibility, targeting and therapeutic abilities [129].…”

“…The coding sequence of the desired ligand is inserted by a gene transfer vector (i.e., lentivirus) between the signal peptide and the N-terminus of the mature peptide of a transmembrane protein. In this way, the parent cells can generate EVs with the peptide of interest on their surface [129]. The candidate protein or peptide, after the transfection in the parent cells, fuses with EVs membrane proteins such as Lamp2b and tetraspanins CD63 and CD9 [43], thus the produced EVs display the just-engineered molecule on their surface.…”