Abstract
RNA interference (RNAi) is a post-transcriptional gene-silencing mechanism that involves the degradation of messenger RNA in a highly sequence-specific manner. Double-stranded small interfering RNA (siRNA), consisting of 21–25 nucleotides, can induce RNAi and inhibit the expression of target proteins. Therefore, siRNA is considered a promising therapeutic for treatment of a variety of diseases, including genetic and viral diseases, and cancer. Clinical trials of siRNA are ongoing or have been planned, although some issues need to be addressed. For example, cellular uptake of naked siRNA is extremely low due to its polyanionic nature. Furthermore, siRNA is easily degraded by enzymes in blood, tissues, and cells. Several types of chemically modified siRNA have been produced and investigated to improve stability; these have involved modification of the siRNA backbone, the sugar moiety, and the nucleotide bases of antisense and/or sense strands. Because the accumulation at the target site after administration is extremely low, even if stability is improved, an effective delivery system is required to induce RNAi at the site of action. Delivery strategies can be categorized into physical methods, conjugation methods, and drug delivery system carrier-mediated methods. Physical techniques can enhance siRNA uptake at a specific tissue site using electroporation, pressure, mechanical massage, etc. Terminal modification of siRNAs can enhance their resistance to degradation by exonucleases in serum and tissue. Moreover, modification with a suitable ligand can achieve targeted delivery. Several types of carrier for drug delivery have been developed for siRNA in addition to traditional cationic liposome and cationic polymer systems. Ultrasound and microbubbles or liposomal bubbles have also been used in combination with a carrier for siRNA delivery. New materials with unique characteristics such as carbon nanotubes, gold nanoparticles, and gold nanorods have attracted attention as innovative carriers for siRNA.
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Acknowledgments
The authors thank all colleagues who have conducted work in this rapidly changing field, and apologize to the colleagues whose work in the field was not directly cited in this review because of space limitations and the highly selective topic.
No funding has been used in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.
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Higuchi, Y., Kawakami, S. & Hashida, M. Strategies for In Vivo Delivery of siRNAs. BioDrugs 24, 195–205 (2010). https://doi.org/10.2165/11534450-000000000-00000
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DOI: https://doi.org/10.2165/11534450-000000000-00000