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Oral delivery of RNAi for cancer therapy

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CANCER AND METASTASIS REVIEWS
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SPRINGER
DOI: 10.1007/s10555-023-10099-x

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Oral RNAi; RNAi therapeutics; Oral medicines; Cancer; Bioengineering

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Cancer is a major global health problem and there is ongoing research to find effective treatments. RNAi has shown promise in targeted therapy, making it an ideal option for cancer treatment. However, oral delivery of RNAi presents challenges such as crossing biological barriers and maintaining stability. Over the years, various approaches have been explored to overcome these challenges. Understanding these challenges and recent advancements is crucial for developing a novel and advanced approach for oral RNAi delivery. In this article, we summarize the delivery strategies and recent developments in oral RNAi delivery, specifically towards preclinical stages.
Cancer is a major health concern worldwide and is still in a continuous surge of seeking for effective treatments. Since the discovery of RNAi and their mechanism of action, it has shown promises in targeted therapy for various diseases including cancer. The ability of RNAi to selectively silence the carcinogenic gene makes them ideal as cancer therapeutics. Oral delivery is the ideal route of administration of drug administration because of its patients' compliance and convenience. However, orally administered RNAi, for instance, siRNA, must cross various extracellular and intracellular biological barriers before it reaches the site of action. It is very challenging and important to keep the siRNA stable until they reach to the targeted site. Harsh pH, thick mucus layer, and nuclease enzyme prevent siRNA to diffuse through the intestinal wall and thereby induce a therapeutic effect. After entering the cell, siRNA is subjected to lysosomal degradation. Over the years, various approaches have been taken into consideration to overcome these challenges for oral RNAi delivery. Therefore, understanding the challenges and recent development is crucial to offer a novel and advanced approach for oral RNAi delivery. Herein, we have summarized the delivery strategies for oral delivery RNAi and recent advancement towards the preclinical stages.

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