Engineering NK Cells with RNA Interference: potential method for cancer treatment
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Alireza Salimi,1 Ali Reza Seddigh,2 Benjamin Babaei,3 Reza Salarinia,4,*
1. Department of Advanced Technologies, School of medicine, North Khorasan University of Medical Science, Bojnurd, Iran
2. Department of Advanced Technologies, School of medicine, North Khorasan University of Medical Science, Bojnurd, Iran
3. Department of Advanced Technologies, School of medicine, North Khorasan University of Medical Science, Bojnurd, Iran
4. Department of Advanced Technologies, School of medicine, North Khorasan University of Medical Science, Bojnurd, Iran
- Introduction: RNA interference (RNAi) strategies include double-stranded RNA (dsRNA), small interfering RNA (siRNA), short hairpin RNA (shRNA), and microRNA (miRNA). RNAi is a potent gene-silencing process that holds great promise in the field of cancer therapy. The discovery of RNAi has generated enthusiasm within the scientific community, not only because it has been used to rapidly identify key molecules involved in numerous disease processes including cancer, but also because RNAi has the potential to be translated into a technology with major therapeutic applications. RNAi is a simple and rapid method of silencing gene expression in a range of organisms. The silencing of a gene is a consequence of degradation of RNA into short RNAs that activate ribonucleases to target homologous mRNA.
Natural killer (NK) cells are innate immune cells endowed with potent cytolytic activity against tumors, and meanwhile act as regulatory cells for the immune system. INHBA encodes an individual from the TGF-β superfamily of proteins and the ligand could be further homo-dimerized to shape activin A or hetero-dimerized to frame inhibin with inhibin beta B . Activin-A impaired human and mouse NK cell proliferation and reduced the production of granzyme B to impair tumor killing. Similar to TGF-, activin-A also induced SMAD2/3 phosphorylation and stimulated NK cells to increase their cell surface expression of several markers of ILC1 cells. So with targeting INHBA by RNAi and prevent the formation of Activin-A, NK cells can do they roles in cancer treatment.
- Methods: Methods: At the First, INHBA sequence collected from NCBI, for design siRNA and shRNA used SSD software. Potential miRNAs which targeting INHBA Were identified by using Targetscan and miRDB databases.
- Results: according to results we identified 7 miRs(hsa-miR-205-5p , hsa-miR-135b-5p, hsa-miR-135a-5p, hsa-miR-22-5p, hsa-miR-509-3p, hsa-miR-20a-5p, hsa-miR-20b-5p) that were Accepted in both of Targetscan and miRDB databases. siRNAs and shRNAs which designed by SSD has shown in table 1and 2). Single-targeting therapies for covid19have been considered to be an effective approach, and RNAi strategy is a better method for gene suppression, and there are many siRNA drugs in clinical trials which two or more genes inhibition simultaneously. At the same time, structurally modified siRNAs .
had been widely used in the RNAi therapeutics development, especially long double-stranded RNAs (dsRNA) were designed for carrying two or more siRNA sequences That targeted more than two parts of one mRNA or more than one mRNA. Current studies have shown that once long dsRNAs get into mammalian cells, they can be used as Dicer’s substrates for siRNAs processing, then the corresponding genes may be possibly inhibited effectively by siRNAs.
- Conclusion: This study has described that has RNAi the potential for cancer treatment. The field of RNAi is still rapidly growing and new discoveries are being made on a daily basis. SiRNAs are currently being used in gene function analysis, target identification and validation and as therapeutic agents. Their potential for use in evaluating target toxicity is significant and warrants further investigation. Although a viable technique for in vitro experimentation, success can still be hampered by challenges with intracellular siRNA delivery and effective gene silencing. Extra researches for choosing the best candidate for siRNA is needed. Choosing the best candidate is one of the critical steps.
- Keywords: RNAi , Natural killer cells , Cancer
