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RNA interference-based therapy and its delivery systems

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Abstract

RNA interference (RNAi) is considered a highly specific approach for gene silencing and holds tremendous potential for treatment of various pathologic conditions such as cardiovascular diseases, viral infections, and cancer. Although gene silencing approaches such as RNAi are widely used in preclinical models, the clinical application of RNAi is challenging primarily because of the difficulty in achieving successful systemic delivery. Effective delivery systems are essential to enable the full therapeutic potential of RNAi. An ideal nanocarrier not only addresses the challenges of delivering naked siRNA/miRNA, including its chemically unstable features, extracellular and intracellular barriers, and innate immune stimulation, but also offers “smart” targeted delivery. Over the past decade, great efforts have been undertaken to develop RNAi delivery systems that overcome these obstacles. This review presents an update on current progress in the therapeutic application of RNAi with a focus on cancer therapy and strategies for optimizing delivery systems, such as lipid-based nanoparticles.

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Acknowledgments

The University of Texas MD Anderson Cancer Center is supported in part by the National Institutes of Health through Cancer Center Support Grant P30CA016672, CA217685, P50 CA098258, UH3 TR000943, U01 CA213759, R35 CA209904), the Ovarian Cancer Research Fund, Inc., CPRIT grant RP120214, DP150091, V-Foundation, the Frank McGraw Memorial Chair in Cancer Research, and the American Cancer Society Research Professor Award.

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Chen, X., Mangala, L.S., Rodriguez-Aguayo, C. et al. RNA interference-based therapy and its delivery systems. Cancer Metastasis Rev 37, 107–124 (2018). https://doi.org/10.1007/s10555-017-9717-6

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