They are suitable for large-scale synthesis, are cost-effective, have low or no immunogenicity, low batch-to-batch variation, and chemical modifications can easily be incorporated for enhanced stability and binding capacity [116]

They are suitable for large-scale synthesis, are cost-effective, have low or no immunogenicity, low batch-to-batch variation, and chemical modifications can easily be incorporated for enhanced stability and binding capacity [116]. acid medicines into EVs. The first is to genetically engineer the parent cell and weight the prospective gene into the EV, and the additional is definitely to isolate EVs and then weight them with the nucleic acid drug. Target organ delivery methods include passive focusing on using the enhanced permeation and retention effect of EVs and active focusing on in which EVs are revised with antibodies, peptides, or aptamers to enhance their build up in tumors. With this review, we summarize the advantages of EVs like a drug delivery system for nucleic acid drugs, the methods of loading nucleic acid medicines into EVs, and the focusing on of EVs to target organs. and focused on ASO4, which was the most effective in decreasing the -synuclein protein level in vitro. EVs loaded with ASO4 showed high cellular uptake and low cytotoxicity in vitro and significantly inhibited -synuclein aggregation. When ASO4 was given to -syn A53T mice, a transgenic mouse model of Parkinsons disease, dopaminergic neuronal degeneration was suppressed, and engine function was significantly improved. In a study on malignant tumors, Xu et al. found that EVs derived from HepG2 cells and loaded with G3139, which is an ASO of BCL-2, significantly reduced BCL-2 manifestation in HepG2 cells [43]. 2.3. miRNAs miRNAs are small RNAs of approximately 20 nucleotides and are CA-074 involved in a variety of physiological processes. miRNAs repress gene manifestation by drawing mRNAs with target sequences into CA-074 the RISC in a manner much like siRNAs. However, in contrast to siRNAs, the acknowledgement of target mRNA by miRNA primarily occurs through foundation pairing between 7 and 8 bases in the 5 end, called the seed sequence, and through complementary sequences that are primarily in the 3 untranslated region (3UTR) of the prospective mRNA [44]. miRNAs can recognize the 5 UTR, introns, and protein-coding regions of mRNAs [45]. Consequently, miRNAs can target a large number of mRNAs, and the same mRNA can be targeted by multiple miRNAs [25,46]. EV-associated miRNAs play a major part in tumor progression through mechanisms such as angiogenesis, immune escape, tumor growth, and premetastatic market formation [47,48]. Consequently, the rules of miRNA manifestation may help to control tumor progression. In addition, the treatment of malignant tumors using miRNA-loaded EVs is definitely a highly analyzed area. Kogure et al. found that EV-associated miR-584 derived from Hep3B cells downregulated transforming growth element beta triggered kinase-1 (TAK-1) [49]. TAK-1 is an upstream member of the mitogen-activated protein kinase kinase kinase family and has an essential part in tumor progression. The authors reported that EV-associated miR-584 inhibited tumor progression in hepatocellular carcinoma. Additional findings showed that EVs loaded with miR-126 mimic inhibited cell proliferation, migration, and invasion in Rabbit Polyclonal to RPAB1 non-small-cell lung carcinoma in vitro and clogged tumor growth in vivo [50]. Mechanistically, miR-126 binds to the integrin alpha-6 (ITGA-6) 3UTR and suppresses ITGA6. ITGA6 reportedly interacts with RPSA to promote cell migration and invasion in pancreatic malignancy [51]. Evidence assisting the delivery of nucleic acid medicines using EVs has been accumulating in recent years. Table 1 summarizes the current knowledge of EV-associated CA-074 oligonucleotide therapy. Nucleic acid medicines are rapidly degraded in the blood circulation, so chemical changes is usually necessary. However, some sequence motifs have undesirable immune reactions or lead to off-target effects [52]. To avoid them, methods for efficiently loading therapeutically effective oligonucleotides into EVs and delivering them.