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Updated: Aug 5, 2025
Bacterial Delivery of RNAi Effectors: Transkingdom RNAi
Published on: August 18, 2010
Oral delivery of RNAi for cancer therapy
Humayra Afrin1,2, Renu Geetha Bai2,3, Raj Kumar2
1Environmental Science & Engineering, University of Texas at El Paso, El Paso, TX, 79965, USA.
Abstract:
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.
Insights
Oral delivery of RNA interference (RNAi) therapeutics, like small interfering RNA (siRNA), faces challenges crossing biological barriers. This review summarizes strategies to enhance oral RNAi delivery for cancer treatment.
Area of Science:
- Biotechnology and Pharmaceutical Sciences
- Molecular Biology and Genetics
- Cancer Therapeutics
Background:
- Cancer remains a significant global health challenge, driving the search for effective treatments.
- RNA interference (RNAi) offers targeted gene silencing, showing promise for cancer therapy.
- Oral drug delivery is preferred for patient compliance but presents significant bioavailability hurdles for RNAi.
Purpose of the Study:
- To review the challenges associated with oral delivery of RNA interference (RNAi) agents, specifically small interfering RNA (siRNA).
- To summarize current strategies and recent advancements in overcoming biological barriers for oral RNAi delivery.
- To provide insights into novel approaches for preclinical development of oral RNAi therapeutics.
Main Methods:
- Comprehensive literature review of studies focusing on oral RNAi delivery systems.
- Analysis of extracellular and intracellular barriers affecting siRNA stability and transport.
- Evaluation of various delivery strategies and their efficacy in preclinical models.
Main Results:
- Oral siRNA faces degradation from harsh gastrointestinal pH, mucus, and nucleases.
- Intracellular barriers, including lysosomal degradation, further impede siRNA therapeutic action.
- Various formulation and delivery strategies are being developed to protect siRNA and enhance its absorption.
Conclusions:
- Overcoming the multifaceted barriers to oral RNAi delivery is critical for its clinical translation.
- Continued research into advanced delivery systems is essential for developing effective oral RNAi cancer therapies.
- Understanding current challenges and advancements is key to innovating future oral RNAi delivery approaches.
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