Login / Signup

Recombinant Technologies Facilitate Drug Metabolism, Pharmacokinetics, and General Biomedical Research.

Joseph CroninAi-Ming Yu
Published in: Drug metabolism and disposition: the biological fate of chemicals (2023)
The development of safe and effective medications requires a profound understanding of their pharmacokinetic (PK) and pharmacodynamic (PD) properties. PK studies have been built through investigation of enzymes and transporters that drive drug absorption, distribution, metabolism, and excretion (ADME). Like many other disciplines, the study of ADME gene products and their functions has been revolutionized through the invention and widespread adoption of recombinant DNA (rDNA) technologies. Recombinant DNA technologies utilize expression vectors such as plasmids to achieve heterologous expression of a desired transgene in a specified host organism. This has enabled the purification of recombinant ADME gene products for functional and structural characterization, allowing investigators to elucidate their roles in drug metabolism and disposition. This strategy has also been utilized to offer recombinant or bioengineered RNA (BioRNA) agents to investigate the posttranscriptional regulation of ADME genes. Conventional research with small noncoding RNAs (ncRNA) such as microRNAs (miRNAs) and small interfering RNAs (siRNAs) has been dependent on synthetic RNA analogs that are known to carry a range of chemical modifications expected to improve stability and PK properties. Indeed, a novel tRNA fused pre-miRNA carrier-based bioengineering platform technology has been established to offer consistent and high-yield production of unparalleled BioRNA molecules from E. coli fermentation. These BioRNAs are produced and processed inside living cells to better recapitulate the properties of natural RNAs, representing superior research tools to investigate regulatory mechanisms behind ADME. Significance Statement In this review article, we summarize recombinant DNA technologies that have been an incredible boon in the study of drug metabolism and pharmacokinetics, providing investigators with powerful tools to express nearly any ADME gene products for functional and structural studies. We further overview novel recombinant RNA technologies and discuss the utilities of bioengineered RNA agents for the investigation of ADME gene regulation and general biomedical research.
Keyphrases