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Barriers of siRNA delivery after systemic administration. Due to extracellular and intracellular barriers, the arrival of siRNA at the target site is complicated. siRNA may be degraded by nucleases in the blood, cleared by kidneys, and taken up by RES, which makes it difficult for siRNA to reach the target site. Even if siRNA reaches the target site, the gene silencing effect may not be exerted due to limited cellular uptake and poor lysosome escape.
