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Compositions and Methods of Using PiRNAs in Cancer Diagnostics and Therapeutics
Patent Number: WO2017147594A1
 
Executive Summary:
  • Invention Type: Therapeutic and Diagnostic
  • Patent Status: Pending
  • Patent Link: https://patents.google.com/patent/WO2017147594A1
  • Research Institute: Yale University
  • Disease Focus: Gliomas, including Glioblastoma
  • Basis of Invention: Approaches for cancer treatment and diagnosis using a novel class of small-RNAs, called PIWI-interacting RNAs (piRNAs)
  • How it works: PIWI-interacting RNAs (piRNAs) are a novel class of RNAs that control both transcriptional and post-transcriptional regulation. Studies have shown that aberrant expression of piRNAs are signatures of cancer. Therefore, this invention suggests methods to exploit piRNAs as therapeutic or diagnostic agents of cancer
  • Lead Challenge Inventor: Yong Zhu
  • Development Stage: Preclinical
  • Novelty:
    • Demonstration that piRNAs have cancer specific in-vitro and in-vivo effects
    • Demonstration that piRNAs have cancer diagnostic applications
  • Clinical Applications:
    •  Treating and diagnosing various types of cancer
 
General Description:
Aberrantly expressed piRNAs, genetically associated piRNAs and their relationship with cancer risk and severity are provided. Compositions and methods of using piRNA for treating cancer are provided. Methods of diagnosing subjects and determining the efficacy of active agents for treating cancer are also provided. Methods of correlating variant piRNA to cancer are also disclosed.
 
Scientific Progress:
In-vitro and in-vivo validation of piRNAs efficiency in reducing cancerous cell and tumor growth. Correlation of aberrant piRNA expression to cancer.
 
Future Directions:
  • Clinical validation
 
Strengths:
  • piRNAs have the following advantages over siRNA and miRNA-based approaches:
    • Higher target specificity due to longer seed sequences
    • Higher tissue specificity since many PIWI proteins are expressed only in tumor cells
    • Can methylate and silence genes
    • High efficacy and lower toxicity
  • piRNAs function in several different cancer models including liver and glioblastoma cancer

​Weaknesses:
  • Competition with more established therapies and tools, such as miRNAs and siRNAs
  • piRNAs are newly discovered, suggesting there may important unknowns about their properties and side effects
 
Patent Status:
Legal status: Pending
  • Priority date: 2016-02-26
  • Filing date: 2017-02-27
  • Publication date: 2017-08-31
 
Publication PMID: 30701019, 27197292, 26210741
 
Publications:
  • Jacobs DI, Qin Q, Fu A, Chen Z, Zhou J, Zhu Y. piRNA-8041 is downregulated in human glioblastoma and suppresses tumor growth in vitro and in vivo. Oncotarget. 2018 Dec 28; 2018 Dec 28.
  • Jacobs DI, Qin Q, Lerro MC, Fu A, Dubrow R, Claus EB, DeWan AT, Wang G, Lin H, Zhu Y. PIWI-Interacting RNAs in Gliomagenesis: Evidence from Post-GWAS and Functional Analyses. Cancer Epidemiol Biomarkers Prev. 2016 Jul; 2016 May 13.
  • Fu A, Jacobs DI, Hoffman AE, Zheng T, Zhu Y. PIWI-interacting RNA 021285 is involved in breast tumorigenesis possibly by remodeling the cancer epigenome. Carcinogenesis. 2015 Oct; 2015 Jul 25.
 
Inventor Bio: Yong Zhu
https://publichealth.yale.edu/people/yong_zhu-1.profile
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Resonance Philanthropies
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