Multifunctional RNA nanoparticles and methods for treating cancer and therapeutic resistant cancer
AssigneesUniversity of Cincinnati, Ohio State Innovation Foundation
InventorsXiaoting Zhang, Peixuan Guo
Life of this patent
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Abstract
RNA nanoparticles functionalized with a HER2-targeting RNA aptamer and at least one MED1 siRNA for targeted delivery of MED1 siRNA to human cancer cells via human epidermal growth factor receptor 2 (HER2) receptors, pharmaceutical compositions of the inventive RNA nanoparticles, and methods for treating breast, HER2-implicated cancers, and in particular therapeutic-resistant cancer such as tamoxifen-resistant breast cancer, by administering pharmaceutical compositions of the inventive RNA nanoparticles.
Claims16
A pRNA nanoparticle functionalized for targeted delivery of Mediator Subunit 1 (MED1) silencing RNA (siRNA) to human cancer cells via human epidermal growth factor receptor 2 (HER2) receptors, the nanoparticle comprising:
- a three-way junction (3-WJ) pRNA, a HER2-targeting RNA aptamer, and two different MED 1 siRNAs, wherein each of the HER-2 targeting RNA aptamer and the MED1 siRNAs is annealed to a separate extending arm of the 3-WJ pRNA, wherein the pRNA nanoparticle is selected from the group consisting of:
- pRNA-HER2mini apt-MED1-siRNA (SEQ ID NO:
- 13),
- pRNA-HER2A1 apt-MED1-siRNA (SEQ ID NO:
- 14),
- pRNA-HER2B3 apt-MED1-siRNA (SEQ ID NO:
- 15),
- pRNA-HER2C3 apt-MED1-siRNA (SEQ ID NO:
- 16),
- pRNA-HER2D3 apt-MED1-siRNA (SEQ ID NO:
- 17), and
- pRNA-HER2E1 apt-MED1-siRNA (SEQ ID NO:
- 18).
A method for treating a human suffering from a cancer selected from breast, uterine, ovarian, stomach, lung, bladder, and salivary cancer, the method comprising administering to the human a pharmaceutical composition comprising at least one pRNA nanoparticle comprising a three-way junction (3-WJ) pRNA, a HER2-targeting RNA aptamer, and two different MED 1 siRNAs, wherein each of the HER-2 targeting RNA aptamer and the MED1 siRNAs is annealed to a separate extending arm of the 3-WJ pRNA.
Dependencies are inferred from the claim text.