# Plant Exosomal Vesicles: Perspective Information Nanocarriers in Biomedicine
## 11 Targeted Gene Regulation via Engineered Exosomes  
The most promising direction might be the investigation of the potential for the use of exosomes in the targeted delivery of genetic material into the cells, particularly when the exosomal vesicles, loaded with the specific microRNA or CRISPR/Cas9, are delivered to regulate the expression of target genes (Figure 4). Although the native miRNAs contained in the plant vesicles are mainly delivered, the exogenous miRNAs and siRNAs (small interfering RNAs) have already been reported to be used for loading exosomes and targeted delivery. Thus, the isolated grapreruit exosomes, passively loaded with siRNAs, are directed against the luciferase reporter gene stably expressed in the GL26-Luc and A549-Luc cell cultures. It has been found that the luciferase siRNAs carried by the grapreruit exosomes and free miRNAs of luciferase gen expression compared to the native plant exosomes and free miRNAs of luciferase itself [120]. In a similar study, the targeting was improved for the grapreruit exosomes by dimethyl sulfoxide [121]. The exosomes were loaded by incubation with therapeutic miRNA17 (miR17), whose genomic target is antigenic peptide MHC-1 expressed on tumor cells. They were injected intranasally into a mouse with a brain tumor GL-26. As a result, mouse survival was increased, probably due to the selective uptake of exosomes by the GL-26 cells, subsequently inhibiting the MHC-1 expression that caused natural killer cells to become activated to kill tumor cells [121]. In another study, exosomes isolated from ginger were loaded with siRNA-CD98 by sonication and administered orally. The exosomes accumulated in the colon and ileum, while free siRNAs as a control were retained only in the stomach, proving the effective targeting of the exosomes to the intestine. In addition, the delivered siRNAs specifically reduced the expression of _CD98_ gene, the excess accumulation of which causes inflammatory bowel disease, attenuated the inflammatory response, and effectively alleviated colitis and cancer associated with colitis [122]. Thus, studies in the field of targeted delivery of miRNAs and siRNAs prove the promise of using the exosomal plant vesicles for this purpose. For mammalian exosomes, the studies \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Plant Species** &
\begin{tabular}{c} **Exosomes** \\ **Characteristics** \\ \end{tabular} & **Therapeutic Effects** & **References** \\ \hline Lemon (_Citrus limon_) & Sizes from 50 to 80 nm & Antitmor activity & [115] \\ \hline Grapreruit (_Citrus paradis_) & The characteristic size is 83 nm the charge is \(-13.9\) mV & Targeted delivery of miRNAs, antimicrobial activity & [57] \\ \hline Ginger (_Zingisher official_) & The characteristic size is 189 nm the charge is \(-5\) mV & Targeted therapeutics delivery, antitumor, hepatoprotective and antimicrobial activity & [116] \\ \hline Wine grape (_Vits vintifera_) & The characteristic size is 37 nm charge in the range from \(-69.6\) mV to +2.52 mV & Antitumor, antimicrobial and regenerative activity, induction of stem cell proliferation & [117] \\ \hline Carrot (_Duacus carota_) & The characteristic size is 150 nm the charge is \(-10.2\) mV & Antioxidant system stimulation, activation of intestinal epithelium regeneration and antimicrobial activity & [104] \\ \hline Wheat (_Tritcium aestivum_) & Sizes from 40 to 100 nm, contain the HSP70 protein & Wound healing & [118] \\ \hline Broccoli (_Brussica glencca_) & Sizes from 18.3 to 118.2 nm the charge is \(-17.1\) mV & Preventive and therapeutic effects on acute and chronic colitis & [113] \\ \hline Asian ginseng (_Pmax ginseng_) & The characteristic size is 92 nm & Anti-aging and anti-pigmentation effect on human dermal fibroblasts and melanocytes & [119] \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Therapeutic effects of plant-derived nanovesicles. on the delivery of the CRISPR/Cas9 system are prevalent.