# Recombinant microRNAs in xenobiotic and nutrient disposition

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $345,237

## Abstract

PROJECT SUMMARY
MicroRNAs (miRNAs or miRs) are genome-derived, functional noncoding RNA (ncRNA) molecules that
govern posttranscriptional regulation of target gene expression in cells. Our long-term objective is to gain a
mechanistic understanding of miRNA-controlled regulation of xenobiotic & nutrient disposition and drug
actions towards the development of new therapeutic strategies. My laboratory pioneered the research on
miRNA pharmacoepigenetics that has offered new insights into inter-individual variability in drug disposition
and response. Since the diseased carcinoma cells are addicted to continuous supply and metabolism of key
xenobiotic nutrients (e.g., amino acids or AAs, vitamins, sugars, etc.) for uncontrolled proliferation and
tumorigenesis, understanding the roles of metabolic enzymes (e.g., pyridoxine-5-prime-phosphate oxidase
or PNPO) and transporters (e.g., AA transporter SLC7A5/LAT1, glucose transporter SLC2A1/GLUT1, etc.)
in nutrient metabolism and transport may help to identify new therapeutic targets. Yet, there is a critical gap
in the understanding of important regulatory factors and mechanisms underlying key nutrients’ disposition
and homeostasis in carcinoma cells. In addition, current research on miRNA functions and therapeutics are
limited to the use of chemo-engineered miRNA “mimics” made in vitro and comprised of extensive and
various types of chemical modifications, which are completely different from natural RNA molecules
produced and folded in living cells without any or just carrying a limited number of posttranscriptional
modifications. This is also in sharp contrast to protein research and therapy that have found ultimate
success by using recombinant or bioengineered proteins produced and folded in living cells, rather than
polypeptides or proteins synthesized chemically in vitro. Very recently, we have established a novel
tRNA/pre-miRNA-based RNA bioengineering technology that permits high-yield and large-scale production
of recombinant miRNA agents through in vivo bacterial fermentation. Our studies have showed that
recombinant miRNAs are biologically active in regulating target gene expression in human cells, and
subsequently modulate drug disposition and response. Furthermore, our preliminary studies have revealed
that particular human tRNA (htRNA) can be coupled with human pre-miRNA (hsa-pre-miR) as novel carriers
for the production of fully-humanized recombinant or bioengineered miRNA agents, namely
hBERA/miRNA. Therefore, in this application, we proposed to (1) establish and utilize novel ncRNA carriers
to produce a collection of recombinant hBERA/miRNA molecules (Aim 1), (2) delineate the mechanistic
actions of recombinant miRNAs in the control of cellular vitamin B6 metabolism and AA
metabolome/homeostasis (Aim 2), and (3) define the effectiveness of recombinant miRNAs in the
modulation of pharmacodynamics in disease animal models in vivo (Aim 3). The proposed research will
establish a one-of-a-kind RNA...

## Key facts

- **NIH application ID:** 10205396
- **Project number:** 9R01CA253230-05A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Aiming Yu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $345,237
- **Award type:** 9
- **Project period:** 2016-03-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10205396

## Citation

> US National Institutes of Health, RePORTER application 10205396, Recombinant microRNAs in xenobiotic and nutrient disposition (9R01CA253230-05A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10205396. Licensed CC0.

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