# Targeted RNA delivery using ribonucleoprotein

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $573,877

## Abstract

ABSTRACT
Silencing RNA (siRNA) is of considerable current interest in medicine because it can elicit potent, target
specific knockdown of virtually any mRNA, creating a useful and proven genetic surrogate tool. Three siRNA-
based therapies have been FDA-approved, while another seven candidates are in phase 3 trials. A key
obstacle limiting the scope of siRNA clinical uses, however, is in vivo targeted delivery, a `chronic' problem that
has plagued the development of virtually all antisense therapies. Recent advances in nanotechnology have
produced many nanocarriers such as cationic lipids, polymers, inorganic nanoparticles, and peptides. Although
the cationic charge is important for siRNA condensation and endosomal escape, it interferes with specific
targeting by non-specifically binding to most proteins and cells. To address this fundamental and chronic
problem, here we propose to further develop a one-of-its-kind RNA nanocarrier for delivery of siRNA cocktails
building on a recent breakthrough we made on human RNA-binding proteins (Corey & Gao Nature BME, PCT
filed, US phase granted). Optimized through millions of years of evolution, these proteins are neutral or slightly
negatively charged yet still binding to cargo RNA tightly and with a very high payload. The absence of
excessive cationic charges is in direct contrast to conventional delivery technologies. Through orientation
controlled self-assembly with siRNA-targeting ligand chimeras, the complex simultaneously achieves all the
desired properties for efficient siRNA delivery and cancer treatment.

## Key facts

- **NIH application ID:** 10833536
- **Project number:** 5R01CA268985-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Xiaohu Gao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $573,877
- **Award type:** 5
- **Project period:** 2023-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833536

## Citation

> US National Institutes of Health, RePORTER application 10833536, Targeted RNA delivery using ribonucleoprotein (5R01CA268985-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10833536. Licensed CC0.

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