Recent Advances in Novel Recombinant RNAs for Studying Post-transcriptional Gene Regulation in Drug Metabolism and Disposition
- PMID: 37170982
- PMCID: PMC10825985
- DOI: 10.2174/1389200224666230425232433
Recent Advances in Novel Recombinant RNAs for Studying Post-transcriptional Gene Regulation in Drug Metabolism and Disposition
Abstract
Drug-metabolizing enzymes and transporters are major determinants of the absorption, disposition, metabolism, and excretion (ADME) of drugs, and changes in ADME gene expression or function may alter the pharmacokinetics/ pharmacodynamics (PK/PD) and further influence drug safety and therapeutic outcomes. ADME gene functions are controlled by diverse factors, such as genetic polymorphism, transcriptional regulation, and coadministered medications. MicroRNAs (miRNAs) are a superfamily of regulatory small noncoding RNAs that are transcribed from the genome to regulate _target gene expression at the post-transcriptional level. The roles of miRNAs in controlling ADME gene expression have been demonstrated, and such miRNAs may consequently influence cellular drug metabolism and disposition capacity. Several types of miRNA mimics and small interfering RNA (siRNA) reagents have been developed and widely used for ADME research. In this review article, we first provide a brief introduction to the mechanistic actions of miRNAs in post-transcriptional gene regulation of drug-metabolizing enzymes, transporters, and transcription factors. After summarizing conventional small RNA production methods, we highlight the latest advances in novel recombinant RNA technologies and applications of the resultant bioengineered RNA (BioRNA) agents to ADME studies. BioRNAs produced in living cells are not only powerful tools for general biological and biomedical research but also potential therapeutic agents amenable to clinical investigations.
Keywords: Drug-metabolizing enzyme; microRNA; recombinant RNA; regulation; siRNA; transporter.
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Conflict of interest statement
CONFLICT OF INTEREST
The authors are named inventors of issued and pending patents related to RNA bioengineering technology and use that are owned by the University of California, Davis; and Dr. Yu is a founder of AimRNA, Inc. that intends to license the intellectual property.
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References
-
- Li AP, Screening for human ADME/Tox drug properties in drug discovery, Drug discovery today, 6 (2001) 357–366. - PubMed
-
- Storelli F, Yin M, Kumar AR, Ladumor MK, Evers R, Chothe PP, Enogieru OJ, Liang X, Lai Y, Unadkat JD, The next frontier in ADME science: Predicting transporter-based drug disposition, tissue concentrations and drug-drug interactions in humans, Pharmacology & Therapeutics, 238 (2022) 108271. - PubMed
-
- DeGorter M, Xia C, Yang J, Kim R, Drug transporters in drug efficacy and toxicity, Annual review of pharmacology and toxicology, 52 (2012) 249–273. - PubMed
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