# Recombinant microRNAs in xenobiotic metabolism and disposition

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $384,999

## Abstract

PROJECT SUMMARY
Understanding the molecular mechanisms behind variable drug metabolism and disposition (DMD) is critical
to improve pharmacotherapy and drug development. The ultimate goal of my research is to decipher novel
posttranscriptional regulation mechanisms controlled by noncoding microRNAs (miRNAs) and establish
their importance in DMD. My laboratory pioneered miRNA research in the fields of DMD that is expected to
fill the critical gaps in understanding new posttranscriptional regulation mechanisms. Nevertheless, current
studies on miRNA functions in DMD, as well as in the broad areas of general medical sciences, are limited to
the use of chemo-engineered RNA “mimics” made in vitro, which, comprised of extensive and various types
of chemical modifications, are fundamentally different from natural RNA molecules that are produced and
folded in cells and do not carry or just have minimal degree of posttranscriptional modifications. This is also
in sharp contrast to protein research that has found the ultimate success by using recombinant or
bioengineered proteins produced and folded in living cells, instead of synthetic polypeptides or proteins
made in vitro. Very recently, we have developed a novel recombinant RNA technology, based upon hybrid
tRNA/pre-miRNA carriers, which offers high-yield and large-scale production of recombinant miRNA agents
(& small interfering RNAs or siRNAs) through cost-effective bacterial fermentation. Our studies have also
demonstrated that bioengineered miRNA agent (BERA) acts as a “prodrug”, which is specifically processed
to target miRNA molecule in human cells to selectively regulate target gene expression. Further, the access
to large quantity (tens milligrams from 1 L bacterial culture) of high-purity (>98%) recombinant miRNA
molecules allows us to readily investigate the impact of miRNAs on pharmacokinetics and
pharmacodynamics (PK/PD) in animal models in vivo. These highly innovative approaches and
one-of-its-kind recombinant miRNA tools shall open up new avenues for miRNA research and development,
as well as broadly general medical sciences. In this MIRA application, we propose to produce and utilize
one-of-a-kind recombinant miRNAs to dissect new regulatory mechanisms in DMD by addressing the
following key questions: 1) Can the tRNA/pre-miRNA-based technology be re-innovated for the production
of fully-humanized recombinant miRNAs (hBERA/miRNAs)? 2) Will hBERA/miRNAs be processed to target
miRNAs in human hepatocytes and liver cells to selectively modulate drug-metabolizing enzyme or
transporter expression, and alter cellular DMD capacity? 3) To what degrees will miRNA alter PK and PD in
the whole-body system?

## Key facts

- **NIH application ID:** 10165376
- **Project number:** 1R35GM140835-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Aiming Yu
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $384,999
- **Award type:** 1
- **Project period:** 2021-06-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165376

## Citation

> US National Institutes of Health, RePORTER application 10165376, Recombinant microRNAs in xenobiotic metabolism and disposition (1R35GM140835-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10165376. Licensed CC0.

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