Splice-Switching Oligonucleotides and Methods of Use
Patent Number: US20180334677A1
Executive Summary:
General Description:
The present disclosure provides methods and compositions for the treatment of cancer. In some aspects, the present disclosure provides splice-switching oligonucleotides that downregulate AR or EGFR expression and methods of using these splice-switching oligonucleotides to treat cancer.
Scientific Progress:
Validation of the inhibition of oncogenic isoforms by splice-switching oligonucleotides in vitro.
Future Directions:
Strengths:
Weaknesses:
Patent Status:
Legal status: Pending
Publication PMID: 30755441
Publication:
Robinson TJ, Freedman JA, Al Abo M, Deveaux AE, LaCroix B, Patierno BM, George DJ, Patierno SR. Alternative RNA Splicing as a Potential Major Source of Untapped Molecular Targets in Precision Oncology and Cancer Disparities. Clin Cancer Res. 2019 Feb 12. pii: clincanres.2445.2018.
Inventor Bio: Jennifer Freedman
https://medicine.duke.edu/faculty/jennifer-freedman-phd
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Pending
- Patent Link: https://patents.google.com/patent/US20180334677A1
- Related Patent Link: https://patents.google.com/patent/WO2017079570A3
- Research Institute: Duke University
- Disease Focus: Brain tumors
- Basis of Invention: Oligonucleotides that modulate splicing of pre-mRNA to control the production of cancer-causing proteins
- How it works: Cancer cells exploit the androgen receptor and epidermal growth factor receptor signaling pathways to grow and develop. Often, mutations in these receptors produce oncogenic isoforms which can result in diseases such as prostate cancer. Thus, limiting the production of these isoforms can result in treatment of these types of cancer. This invention uses splice-switching oligonucleotides to control the expression of the oncogenic isoforms by modulating the splicing of the pre-mRNA of the receptors
- Lead Challenge Inventor: Jennifer Freedman
- Inventors: Jennifer Freedman, Brendon Patierno, Bonnie Lacroix, Timothy Robinson, Bruce Sullenger, Daniel George, Steven Patierno
- Development Stage: Lead Optimization
- Novelty:
- The use of oligonucleotides to alter splicing of oncogenic isoforms of the androgen and the epidermal growth factor receptor, thereby inhibiting the production of the oncogenic proteins
- Clinical Applications:
- Treating cancer, particularly cancers that use the androgen receptor and epidermal growth factor receptor pathways
General Description:
The present disclosure provides methods and compositions for the treatment of cancer. In some aspects, the present disclosure provides splice-switching oligonucleotides that downregulate AR or EGFR expression and methods of using these splice-switching oligonucleotides to treat cancer.
Scientific Progress:
Validation of the inhibition of oncogenic isoforms by splice-switching oligonucleotides in vitro.
Future Directions:
- Preclinical testing in rodent models; clinical validation in humans
Strengths:
- Easy to synthesize
- Inhibit expression of oncogenic isoforms and correct isoforms producing therapeutic proteins
Weaknesses:
- Competition with other therapeutics targeting the androgen and epidermal growth factor receptors
- Lack of in vivo data measuring how molecule will behave inside of an organism
Patent Status:
Legal status: Pending
- Priority date: 2015-11-04
- Filing date: 2016-11-04
- Publication date: 2018-11-22
Publication PMID: 30755441
Publication:
Robinson TJ, Freedman JA, Al Abo M, Deveaux AE, LaCroix B, Patierno BM, George DJ, Patierno SR. Alternative RNA Splicing as a Potential Major Source of Untapped Molecular Targets in Precision Oncology and Cancer Disparities. Clin Cancer Res. 2019 Feb 12. pii: clincanres.2445.2018.
Inventor Bio: Jennifer Freedman
https://medicine.duke.edu/faculty/jennifer-freedman-phd
