Pharmaceutical composition comprising NANOG SHRNA, and method of using NANOG SHRNA to treat cancer
Inventors
Jessup, John Milburn • Zhang, Jingyu
Assignees
US Department of Health and Human Services
Publication Number
US-9163236-B2
Publication Date
2015-10-20
Expiration Date
2031-12-06
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
The present description relates to an inhibitory RNA molecule, comprising an oligonucleotide that selectively knocks down expression of either Nanog or a Nanog pseudogene, a vector capable of encoding such inhibitory RNA molecule, pharmaceutical compositions comprising said vector, and methods of treating cancer by administration of said pharmaceutical composition.
Core Innovation
The invention relates to an inhibitory RNA molecule comprising an oligonucleotide that selectively knocks down expression of either Nanog or a Nanog pseudogene, including NanogP8. It includes viral vectors capable of encoding such inhibitory RNA molecules, pharmaceutical compositions comprising the vectors, and methods of treating cancer by administering these pharmaceutical compositions.
The issue addressed is the need for effective therapeutics to prevent and treat colorectal carcinoma (CRC), which has a high mortality rate. Nanog, a core embryonic stem cell gene, and its pseudogenes have been implicated in cancer stem cell functions and tumor development, but their roles in tumorigenesis and metastasis in various cancers including CRC remain unclear.
The invention provides allele-specific shRNAs that target Nanog or NanogP8 selectively, thereby inhibiting cancer cell proliferation, inducing apoptosis, and reducing tumor mass and metastatic potential. The approach uses lentiviral vectors and lipid-based delivery systems for efficient administration to cancer cells, particularly for colorectal cancer. Methods to monitor and evaluate the efficacy of these RNA molecules and vectors in vitro and in vivo are also described.
Claims Coverage
The patent contains two independent claims directed to inhibitory RNA molecules and viral vectors comprising such molecules, each with specific sequences for targeting Nanog or NanogP8.
Inhibitory RNA molecules targeting Nanog or NanogP8
RNA molecules comprising oligonucleotides that knock down expression of either Nanog or NanogP8, specifically sequences of SEQ ID NO:3 or SEQ ID NO:37, or alternatively SEQ ID NO:8 or SEQ ID NO:34.
Viral vectors encoding inhibitory RNA molecules
Viral vectors carrying the inhibitory RNA molecules capable of transducing cancer cells and inducing apoptosis, inhibiting proliferation, or reducing tumor mass, with packaging allowing targeting to colorectal carcinoma cells and overexpression of RNA inhibiting Nanog or NanogP8 expression.
Pharmaceutical compositions comprising viral vectors or inhibitory RNA
Pharmaceutical compositions that include viral vectors or inhibitory RNA molecules (including double stranded siRNA) capable of inhibiting Nanog or NanogP8 expression, for use in treating cancer by administration to patients.
The independent claims cover the inhibitory RNA molecules specifically targeting Nanog or NanogP8 sequences, viral vectors encoding these RNA molecules with capabilities to treat cancer by affecting cancer cell behavior, and pharmaceutical compositions containing these vectors or RNA molecules for therapeutic application.
Stated Advantages
The inhibitory RNA molecules and viral vectors can specifically knock down Nanog or NanogP8 expression without affecting the alternate gene, allowing targeted therapy.
Delivery via lentiviral vectors or lipid particles enables effective transduction of cancer cells, including colorectal cancer cells.
The compositions can induce apoptosis in cancer cells, inhibit cancer cell proliferation, reduce tumor mass, and block metastasis, showing multifunctional therapeutic potential.
Documented Applications
Treatment of colorectal carcinoma (CRC) by administering pharmaceutical compositions comprising inhibitory RNA molecules targeting Nanog or NanogP8.
Use of lentiviral vectors to deliver allele-specific shRNA to cancer cells to reduce tumor growth and metastasis.
Application in treating cancers with malignant phenotypes, including cancer cells capable of metastasizing, demonstrated in xenograft models and experimental metastasis assays.
Potential treatment of other cancers such as gastric, breast, glioblastoma, and cervical cancers via similar RNA interference strategies.
Interested in licensing this patent?