Exosome-Based COVID-19 Vaccine.

Extracellular vesicles (EVs) enable cell-to-cell communication and, by delivering antigens, can stimulate the immune response strongly. Approved in use SARS-CoV-2 vaccine, candidates immunize with the viral spike protein delivered via viral vectors, translated by injected mRNAs, or as a pure protein. Here, we outline a novel methodological approach for generating SARS-CoV-2 vaccine using exosome that delivers antigens from the SARS-CoV-2 structural proteins. Engineered EVs can be loaded with viral antigens, thus acting as antigens presenting EVs, eliciting strong and targeted CD8(+) T cell and B cell, offering a unique approach to vaccine development. Engineered EVs thus portray a safe, adaptable, and effective approach for a virus-free vaccine development.

Exosomal delivery of TRAIL and miR­335 for the treatment of hepatocellular carcinoma (Review).

Liver cancer is the sixth most prevalent type of cancer worldwide and accounts for the third most frequent cause of cancer­associated mortality. Conventional anticancer drugs display limited efficacy owing to their short half­life, poor solubility and inefficient drug delivery. Despite advancements being made in drug discovery and development for the treatment of hepatocellular carcinoma (HCC), drug inefficacy and drug continue to pose significant obstacles to effective treatment. Therefore, it is imperative that novel treatment strategies be developed with the aim of developing anticancer treatments without any side­effects and with long­term durability. Extracellular vesicles, such as exosomes, intercellular communication agents which have the ability to carry heterogenous molecules with high penetrability, low immunogenicity and longer durability, may provide a versatile natural delivery system. The present review article illustrates the innovative treatment strategy using exosomes as a delivery agent for two distinct anticancer candidates, i.e., tumor necrosis factor­related apoptosis­inducing ligand and microRNA­335. The aim of the present review was to present a unique strategy for the development of an exceptional anticancer treatment therapy exploiting exosomes as a delivery vehicle which may be used for HCC.

Transforming growth factor­ß family and stem cell­derived exosome therapeutic treatment in osteoarthritis (Review).

Osteoarthritis (OA), although extensively researched, still lacks an effective and safe treatment. The only current treatment option available for advanced OA is joint replacement surgery. This surgery may pose the risks of persistent pain, surgical complications and limited implant lifespan. Transforming growth factor (TGF)­ß has a crucial role in multiple cellular processes such as cell proliferation. Any deterioration in TGF­ß signaling pathways can have an immense impact on OA. Owing to the crucial role of TGF­ß in cartilage homeostasis, targeting it could be an alternative therapeutic approach. Additionally, stem cell­based therapy has recently emerged as an effective treatment strategy that could replace surgery. A number of recent findings suggest that the tissue regeneration effect of stem cells is attributed to the paracrine secretion of anti­inflammatory and chondroprotective mediators or trophic factors, particularly nanosized extracellular vesicles (i.e., exosomes). Literature searches were performed in the MEDLINE, EMBASE, Cochrane Library and PubMed electronic database for relevant articles published before September 2021. Multiple investigators have confirmed TGF­ß3 as a promising candidate which has the chondrogenic potential to repair articular cartilage degeneration. Combining TGF­ß3 with bone morphogenetic proteins­6, which has synergistic effect on chondrogenesis, with an efficient platform such as exosomes, which themselves possess a chondroprotective function, offers an innovative and more efficient approach to treat injured cartilage. In addition, multiple findings stating the role of exosomes in chondroprotection has also verified a similar fact showing exosomes may be a more favorable choice than the source itself. In the present review, the importance of TGF­ß family in OA and the possibility of therapeutic treatment using stem cell­derived exosomes are described.

Possibility of exosome­based coronavirus disease 2019 vaccine (Review).

Coronavirus disease 2019 (COVID­19) is a global pandemic that can have a long­lasting impact on public health if not properly managed. Ongoing vaccine development trials involve classical molecular strategies based on inactivated or attenuated viruses, single peptides or viral vectors. However, there are multiple issues, such as the risk of reversion to virulence, inability to provide long­lasting protection and limited protective immunity. To overcome the aforementioned drawbacks of currently available COVID­19 vaccines, an alternative strategy is required to produce safe and efficacious vaccines that impart long­term immunity. Exosomes (key intercellular communicators characterized by low immunogenicity, high biocompatibility and innate cargo­loading capacity) offer a novel approach for effective COVID­19 vaccine development. An engineered exosome­based vaccine displaying the four primary structural proteins of SARS­CoV­2 (spike, membrane, nucleocapside and envelope proteins) induces humoral and cell mediated immunity and triggers long­lasting immunity. The present review investigated the prospective use of exosomes in the development of COVID­19 vaccines; moreover, exosome­based vaccines may be key to control the COVID­19 pandemic by providing enhanced protection compared with existing vaccines.