# Novel biologic RNA molecules to modulate HCC metabolism

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $483,591

## Abstract

PROJECT SUMMARY
Liver cancer is a major cause of cancer-related deaths within the United States, being the fifth and seventh
leading cause of cancer deaths among men and women, respectively. There is a high demand for new and
more effective therapeutics for the treatment of liver cancer, especially for the most common hepatocellular
carcinoma (HCC), with an improved understanding of vital regulatory factors underlying HCC cell
metabolism essential for tumor progression. Genome-derived noncoding microRNAs (miRNAs or miRs)
have been revealed as critical elements to control posttranscriptional gene regulation, and restoration of
liver-enriched, oncolytic miRNAs (e.g., let-7-5p isoforms, miR-122-5p, and miR-148a-3p) lost or
downregulated in HCC cells represents a new therapeutic strategy. However, current miRNA functional and
experimental therapeutic studies are limited to the use of miRNA mimics chemo-engineered in vitro and
comprised of extensive and various types of artificial modifications, which are totally different from natural
miRNA molecules produced in vivo. This is also in sharp contrast to protein research and therapy in which
bioengineered or recombinant protein agents produced and folded in vivo, rather than synthetic
polypeptides or proteins made in vitro, have been used and found enormous success. To overcome this
barrier, the PI has recently developed a novel RNA molecular bioengineering platform technology,
based upon specific hybrid tRNA/pre-miRNA molecules identified in the PI’s lab as carriers, to achieve
high-yield and large-scale, in vivo fermentation production of true biologic or bioengineered RNA
(BioRNA) molecules for basic and translational research. Our following studies have demonstrated that
miRNA (e.g., let-7c-5p) is selectively released from BioRNA “prodrug” in human HCC cells to regulate target
gene expression (LIN28B) and control cellular processes (tumorsphere formation), and
liposome-polyethylenimine (LPP) nanocomplex is superior to in vivo-jetPEI to deliver BioRNA into
orthotopic HCC tissues and inhibit tumor growth in mouse models. Our further efforts have led to the
identification of proper human tRNAs to couple with human hsa-pre-miRNAs as new carriers to offer
humanized BioRNAs to target HCC. In addition, humanized BioRNA/miR-148a-3p is precisely processed
to miR-148a-3p in human HCC cells to modulate specific amino acid and glucose transporter expression
towards the control of aminolyses and glycolysis. Given these exciting preliminary findings, we hypothesize
that novel, HCC-targeted, humanized BioRNAs can be bioengineered and used to dissect HCC nutrient
homeostasis and tumor metabolism. To test the hypothesis, we proposed to (i) design, clone, express, and
purify a focused group of novel humanized BioRNAs for the inhibition of HCC cell viability (Aim 1), (ii)
delineate the mechanistic actions of BioRNAs in the control of HCC cell metabolism (Aim 2), and (iii)
establish the effectiveness and safety of can...

## Key facts

- **NIH application ID:** 10936391
- **Project number:** 1R01CA291771-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Aiming Yu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $483,591
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10936391

## Citation

> US National Institutes of Health, RePORTER application 10936391, Novel biologic RNA molecules to modulate HCC metabolism (1R01CA291771-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10936391. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*