RNA nanotechnology has progressed rapidly during the past several years. This nanotechnology includes the integration of multiple functional modules into one nanoparticle, of which the scaffolds, ligands, therapeutics, and regulators can be composed mainly or exclusively of RNA. We have constructed RNA nanoparticles of diverse size, shape, and stoichiometry displaying high chemical and thermodynamic stability and demonstrated their ability to harbor different functional groups, such as siRNA, miRNA, ribozyme, drug, and cancer targeting RNA aptamer. All functional modules retain their authentic folding and independent functionalities for specific cell binding, gene silencing, and cancer targeting in vivo. Upon systemic injection in tumor bearing mice, RNA nanoparticles bind to xenograft and metastatic tumors specifically and strongly with little to no accumulation in healthy vital organs and tissues 3-4 hours post-administration. The RNA nanoparticles are non-toxic and display favorable biodistribution and pharmacokinetic profiles. Our long-term goal is to promote RNA nanoparticles as a new generation of drug for the treatment of cancers in the clinic. The short-term goal of this project is to characterize the behavior of RNA nanoparticles in vitro and in vivo, with an aim to improve the efficiency for specific cell targeting, internalization and intracellular trafficking, favorable biodistribution without entrapment in liver, endosome escape, and tumor regression. These studies are based on three central hypotheses: (1) intracellular trafficking pathways and endosome escape are critical for effective cancer therapy; (2) biodistribution and pharmacological profiles of RNA nanoparticles are shape and size dependent; and, (3) immune responses elicited by RNA nanoparticles are highly dependent on RNA sequence, chemical modifications, size, shape, and stoichiometry. To address our goals, we will (1) systemically dissect the intracellular pathways taken by RNA nanoparticles and enhance their endosome escape capabilities; (2) inspect the pharmacokinetics (PK); pharmacodynamics (PD); and biodistribution of RNA nanoparticles with the goal of enhancing cancer targeting with minimal accumulation in healthy organs; and, (3) evaluate the immune responses of RNA nanoparticles to minimize non-specific side effects, as well as develop methods to stimulate the immune system by incorporating immuno-stimulatory modules to RNA nanoparticles for cancer immunotherapy. Upon completion of these pre-clinical studies, we will have identified several RNA nanoparticles with optimized shape, size, and stoichiometry displaying favorable safety profiles and high therapeutic efficacy to comply with FDA Investigational New Drug guidelines for initiating clinical trials.

Public Health Relevance

The goal of this project is to identify and optimize RNA nanoparticles for enhanced cancer targeting, reduced healthy organ accumulation, and higher efficiency in endosome escape for effective cancer treatment. Accordingly, we will investigate the size, shape and chemical attributes of RNA nanoparticles in clinically relevant cancer mouse models focusing on intracellular trafficking, biodistribution, endosome escape, pharmacodynamics, pharmacokinetics, and immune responses.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZCA1-TCRB-D (M1))
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Hartshorn, Christopher
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Ohio State University
Schools of Pharmacy
United States
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Shu, Yi; Yin, Hongran; Rajabi, Mehdi et al. (2018) RNA-based micelles: A novel platform for paclitaxel loading and delivery. J Control Release 276:17-29
Shi, Zhanquan; Li, S Kevin; Charoenputtakun, Ponwanit et al. (2018) RNA nanoparticle distribution and clearance in the eye after subconjunctival injection with and without thermosensitive hydrogels. J Control Release 270:14-22
Xu, Congcong; Haque, Farzin; Jasinski, Daniel L et al. (2018) Favorable biodistribution, specific targeting and conditional endosomal escape of RNA nanoparticles in cancer therapy. Cancer Lett 414:57-70
Jasinski, Daniel L; Li, Hui; Guo, Peixuan (2018) The Effect of Size and Shape of RNA Nanoparticles on Biodistribution. Mol Ther 26:784-792
Guo, Sijin; Piao, Xijun; Li, Hui et al. (2018) Methods for construction and characterization of simple or special multifunctional RNA nanoparticles based on the 3WJ of phi29 DNA packaging motor. Methods 143:121-133
Pi, Fengmei; Binzel, Daniel W; Lee, Tae Jin et al. (2018) Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression. Nat Nanotechnol 13:82-89
Haque, Farzin; Pi, Fengmei; Zhao, Zhengyi et al. (2018) RNA versatility, flexibility, and thermostability for practice in RNA nanotechnology and biomedical applications. Wiley Interdiscip Rev RNA 9:
Piao, Xijun; Wang, Hongzhi; Binzel, Daniel W et al. (2018) Assessment and comparison of thermal stability of phosphorothioate-DNA, DNA, RNA, 2'-F RNA, and LNA in the context of Phi29 pRNA 3WJ. RNA 24:67-76
Jasinski, Daniel L; Yin, Hongran; Li, Zhefeng et al. (2018) Hydrophobic Effect from Conjugated Chemicals or Drugs on In Vivo Biodistribution of RNA Nanoparticles. Hum Gene Ther 29:77-86
Haque, Farzin; Xu, Congcong; Jasinski, Daniel L et al. (2017) Using Planar Phi29 pRNA Three-Way Junction to Control Size and Shape of RNA Nanoparticles for Biodistribution Profiling in Mice. Methods Mol Biol 1632:359-380

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