Oral delivery of RNAi for cancer therapy

Humayra Afrin, Renu Geetha Bai, Raj Kumar, Sheikh Shafin Ahmad, Sandeep K. Agarwal, Md Nurunnabi

Research output: Contribution to journalReview articlepeer-review

22 Scopus citations

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.

Original languageEnglish
Pages (from-to)699-724
Number of pages26
JournalCancer and Metastasis Reviews
Volume42
Issue number3
Early online date27 Mar 2023
DOIs
StatePublished - Sep 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Funding

We acknowledge the funding by the Cancer Prevention Research Institute of Texas (CPRIT) through the Texas Regional Excellence in Cancer Award (TREC) under Award No. PR210153, and National Institutes of Health (NIH) under Award No R03OD032624. The contents of this paper are solely the authors’ responsibility and do not necessarily represent the official views of NIH.

FundersFunder number
Texas Regional Excellence in Cancer AwardPR210153
National Institutes of HealthR03OD032624
Cancer Prevention and Research Institute of Texas

    Keywords

    • Bioengineering
    • Cancer
    • Oral RNAi
    • Oral medicines
    • RNAi therapeutics

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