# Overcoming Breast Cancer Therapeutic Resistance by Multifunctional RNA Nanoparticles

> **NIH NIH R41** · RNA NANOTHERAPEUTICS LLC · 2022 · $406,500

## Abstract

Project Summary
Breast cancer is one of the most frequent cancers and leading causes of death for women in the
U.S. with an estimated 287,850 new diagnoses of invasive breast cancer and 43,250 deaths in 2022. The vast
majority (75%) of breast cancer is estrogen receptor-positive (ER+) breast cancer but unfortunately, about 50%
of them become resistant and fail to respond to the current anti-estrogen therapies. There are currently no
effective treatment approaches available for these therapeutic resistant breast cancer and patients often rely
on highly toxic chemo- and radiation therapies, etc. Thus, the development of new and improved targeted
treatment to overcome resistance and minimize side effects is urgently needed. Recent work has
established tissue-specific ER coactivator MED1 as a key anti-estrogen treatment resistance gene in breast
cancer. Importantly, MED1 is overexpressed in about 50% of all breast cancers and clinical evidence indicates
that MED1 expression highly correlates with poor disease-free survival of breast cancer patients. RNA
Nanotherapeutics and its research partners at the University of Cincinnati have developed an innovative
patented RNA nanotechnology-based approach to target MED1 in breast cancer cells to overcome treatment
resistance. These highly stable multifunctional RNA nanoparticles have been successfully tested in in vitro and
in vivo preclinical models and exhibited highly desirable tumor-specific targeting and treatment efficacy with no
apparent toxicity. In this Phase I STTR, RNA Nanotherapeutics, in collaboration with its research partners at
the University of Cincinnati and an oligonucleotide therapeutics CMC/strategy consultant, will carry out the
following specific aims: 1) test the efficacy of the pRNA-HER2apt-siMED1 nanoparticles in vivo in breast
cancer patient-derived xenograft (PDX) models; and 2) assess the safety and toxicity of the pRNA-HER2apt-
siMED1 nanoparticles in vivo. We expect successful completion of these proposed studies will provide the
results and data needed for our Phase II efforts and further engagement with private-sector investors to carry
out IND enabling studies for clinical trials. With the recent increased FDA approvals and broad use of RNA-
based vaccines and medicines, we fully anticipate that our RNA nanotechnology-based product represents a
highly promising next-generation therapy to benefit breast cancer patient care and beyond.

## Key facts

- **NIH application ID:** 10600748
- **Project number:** 1R41CA277939-01
- **Recipient organization:** RNA NANOTHERAPEUTICS LLC
- **Principal Investigator:** Xiaoting Zhang
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $406,500
- **Award type:** 1
- **Project period:** 2022-09-07 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10600748

## Citation

> US National Institutes of Health, RePORTER application 10600748, Overcoming Breast Cancer Therapeutic Resistance by Multifunctional RNA Nanoparticles (1R41CA277939-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10600748. Licensed CC0.

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