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Principal Investigator: Xiaoting Zhang
Organization: RNA NANOTHERAPEUTICS LLC
Fiscal Year: 2022
Award: $406,500
Funding agency: National Cancer Institute
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.
Terms: <After Care><After-Treatment><Aftercare><American Cancer Society><Animals><Anti-Estrogens><Antiestrogen Therapy><Behavior><Biologic Products><Biological Agent><Biological Products><Blood Serum><Body Tissues><Body Weight><Body Weight decreased><Breast Cancer><Breast Cancer Cell><Breast Cancer Patient><Breast Cancer Treatment><Breast Cancer cell line><Breast Cancer therapy><Breast Neoplasms><Breast PDX models><Breast Tumor Patient><Breast Tumors><Breast tumor cell line><Cancers><Cause of Death><Cessation of life><Clinical><Clinical Trials><Collaborations><Data><Death><Development><Diagnosis><Disease><Disease-Free Survival><Disorder><Doctor of Philosophy><Dose><ER Positive><ER+><ERBB2><ERBB2 gene><Estrogen Antagonists><Estrogen receptor positive><Event-Free Survival><Exhibits><Faslodex><Femara><Fulvestrant><Gene Expression><Grant><HER -2><HER-2><HER2><HER2 Genes><HER2/neu><Heart><Hematology><Heterograft><Heterologous Transplantation><Histology><Human><ICI 182,780><ICI 182780><In Vitro><Inflammatory><Kidney><Kidney Urinary System><Knowledge><Lead><Legal patent><Letrozole><Licensing><Ligands><Liver><Malignant Neoplasms><Malignant Tumor><Mammary Cancer><Mammary Neoplasms><Measures><Mediating><Medicine><Metastasis><Metastasis to the Lung><Metastasize><Metastatic Lesion><Metastatic Mass><Metastatic Neoplasm><Metastatic Neoplasm to the Lung><Metastatic Tumor><Metastatic Tumor to the Lung><Mice><Mice Mammals><Mission><Modern Man><Molecular><Monitor><Murine><Mus><NEU Oncogene><NEU protein><NIH><Nanotechnology><National Institutes of Health><Neoplasm Metastasis><Non-Polyadenylated RNA><Oligo><Oligonucleotides><Oncogene ErbB2><PDX model><Patents><Pathway interactions><Patient Care><Patient Care Delivery><Patient derived xenograft><Patient-derived xenograft models of breast cancer><Pb element><Persons><Ph.D.><PhD><Phase><Physiologic><Physiological><Pre-Clinical Model><Preclinical Models><Private Sector><Property><Public Health><RNA><RNA Gene Products><RNA targeting drug><RNA targeting therapeutics><RNA vaccine><RNA-based vaccine><RNA-targeting therapy><Radiation therapy><Radiotherapeutics><Radiotherapy><Refractory><Research><Resistance><Ribonucleic Acid><STTR><Safety><Scientific Advances and Accomplishments><Secondary Neoplasm><Secondary Tumor><Serum><Short interfering RNA><Small Business Technology Transfer Research><Small Interfering RNA><Spinal Column><Spine><TKR1><Tamoxifen><Technology><Testing><Therapeutic><Tissues><Toxic effect><Toxicities><Toxicokinetics><Treatment Efficacy><United States National Institutes of Health><Universities><Vertebral column><Weight Loss><Weight Reduction><Woman><Work><Xenograft><Xenograft procedure><Xenotransplantation><anti-cancer research><anti-estrogen therapy><anticancer research><antiestrogen><antiestrogenic><aptamer><backbone><base><biologics><biopharmaceutical><biotherapeutic agent><body weight loss><breast cancer PDX><breast cancer patient-derived xenograft><breast tumor cell><c-erbB-2><c-erbB-2 Genes><c-erbB-2 Proto-Oncogenes><cancer metastasis><cancer progenitor cells><cancer research><cancer stem cell><commercialization><developmental><effective therapy><effective treatment><efficacy testing><erbB-2 Genes><estrogen inhibitor><heavy metal Pb><heavy metal lead><hepatic body system><hepatic organ system><herstatin><immunogenicity><improved><in vivo><innovate><innovation><innovative><intervention efficacy><lung metastasis><mRNA vaccine><mRNA-based vaccine><malignancy><malignant breast neoplasm><malignant breast tumor><malignant stem cell><mammary tumor><metastasize to the lung><mortality><mouse model><murine model><nano particle><nano tech><nano technology><nano therapeutic><nano-sized particle><nano-technological><nanoparticle><nanosized particle><nanotech><nanotechnological><nanotherapeutic><neoplasm/cancer><neu Genes><new drug treatments><new drugs><new therapeutics><new therapy><next generation><next generation therapeutics><novel><novel drug treatments><novel drugs><novel therapeutics><novel therapy><oligos><overexpress><overexpression><pathway><patient derived xenograft model><post treatment><pulmonary metastasis><radiation treatment><renal><resistance gene><resistance locus><resistance to therapy><resistant><resistant gene><resistant to therapy><scientific accomplishments><scientific advances><self assembly><siRNA><side effect><small molecule><success><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><therapeutic efficacy><therapeutic resistance><therapy efficacy><therapy resistant><treatment resistance><treatment with radiation><tumor><tumor cell metastasis><tumor growth><wt-loss><xeno-transplant><xeno-transplantation>