Oral delivery of RNAi for cancer therapy

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.

Recent insights into breast milk microRNA: their role as functional regulators

“…Understanding this process could facilitate the development of artificially modified milk compositions containing a more balanced array of miRNAs, thus potentially enhancing infant development. it provides a natural solution that surpasses the traditional use of artificial nanoparticles as carriers for RNA interference (RNAi) drugs ( 26 , 57 ). Once it is confirmed that BM miRNAs are functional regulators, more comprehensive testing of commercial milk may need to be considered to ensure the quality of commercial milk at the molecular level ( 61 ).…”

“…This resilience could be attributed to the protective role of milk exosomes ( 25 ), suggesting a potential way for drug delivery. Besides, before internalization, miRNA must cross several physical barriers, including the gastrointestinal (GI) tract and its mucus layer ( 26 ). Regarding the protective mechanisms, several studies have proposed different theories.…”

β-Glucan-Mediated Oral Codelivery of 5FU and Bcl2 siRNA Attenuates Stomach Cancer

“…Therefore, we aim to incorporate a Bcl2 small interfering RNA (siRNA) that holds emerging promise for the genetic treatment of cancer. Since its discovery, siRNA has been considered to be applied as gene therapy for treatments of various cancers including stomach cancer. , …”

What is the role of microbial biotechnology and genetic engineering in medicine?

“…Since RNAi technology shows a high specificity towards mRNA binding, allowing differentiation between mRNAs with only one genetic point mutation (Acunzo et al, 2017;Ohnishi et al, 2008) (Di Nunno et al, 2023). Thus, in overall, live-therapeutic bacteria (Figure 3) constitute a very promising alternative approach to treating a broad array of diseases, including cancer, and might reduce the problems derived from prolonged treatment generated with the classical systemically administered therapies, such as reduced efficacy and toxicity (Afrin et al, 2023).…”