IMPORTANCE: Our study revealed that the components of DNA virus could be packaged and transmitted through the exosomes of lower invertebrates, which strongly demonstrated the diversity of exosome-mediated viral immunity and its universality in animals. Furthermore, we elucidated the mechanism of apoptotic signal transduction between cells from the perspective of exosomes and revealed a novel strategy for the host to cope with viral infection.
AREAS COVERED: The steps involved in preparing the mRNA-based cancer vaccines are isolation of the mRNA cancer from the target protein using the nucleic acid RNA-based vaccine, sequence construction to prepare the DNA template, in vitro transcription for protein translation from DNA into mRNA strand, 5' cap addition and poly(A) tailing to stabilize and protect the mRNA from degradation and purification process to remove contaminants produced during preparation.
EXPERT OPINION: Lipid nanoparticles, lipid/protamine/mRNA nanoparticles, and cell-penetrating peptides have been used to formulate mRNA vaccine and to ensure vaccine stability and delivery to the target site. Delivery of the vaccine to the target site will trigger adaptive and innate immune responses. Two predominant factors of the development of mRNA-based cancer vaccines are intrinsic influence and external influence. In addition, research relating to the dosage, route of administration, and cancer antigen types have been observed to positively impact the development of mRNA vaccine.
METHODS: Chemotaxis was evaluated using a modified Boyden chamber and phagocytosis was determined by flowcytometer. Respiratory burst was investigated by luminol-based chemiluminescence assay while MPO activity was determined by colorimetric assay.
KEY FINDINGS: Artocarpanone and artocarpin strongly inhibited all steps of phagocytosis. Artocarpanone and artocarpin showed strong chemotactic activity with IC50 values of 6.96 and 6.10 μm, respectively, which were lower than that of ibuprofen (7.37 μm). Artocarpanone was the most potent compound in inhibiting ROS production of polymorphonuclear leucocytes and monocytes with IC50 values comparable to those of aspirin. Artocarpin at 100 μg/ml inhibited phagocytosis of opsonized bacteria (28.3%). It also strongly inhibited MPO release with an IC50 value (23.3 μm) lower than that of indomethacin (69 μm). Structure-activity analysis indicated that the number of hydroxyl group, the presence of prenyl group and variation of C-2 and C-3 bonds might contribute towards their phagocytosis.
CONCLUSIONS: Artocarpanone and artocarpin were able to suppress strongly the phagocytosis of human phagocytes at different steps and have potential to be developed into potent anti-inflammatory agents.