MicroRNA Therapeutics for Augmenting Blood Vessel Growth
Agents that enhance the expression of this miRNA may allow the treatment of diseases with excessive neovascularization and agents that inhibit this miRNA expression may be used to treat diseases with insufficient neovascularization.The specific mode of action is particularly well-suited for combination therapy with standard genotoxic chemotherapies or radiation to improve outcome for cancer and by enhanced killing of endothelial cells and decrease tumor angiogenesis.
Increasing levels of this miRNA blocks angiogenesis, which may treat disease, such as cancer, retinal age-related macular degeneration, diabetic retinopathy and inflammatory diseases, including rheumatoid arthritis, psoriasis, and fibrosis. This technology may be particularly suited for ocular disorders where route of administration is favorable. Conversely, blocking the activity of this miRNA encourages blood vessel growth, which may treat cardiovascular, thrombotic and ischemic diseases, including stroke and myocardial infarction.
UCSD inventors used differential screens of HUVEC cells to identify specific miRNAs that are significantly altered in response to genotoxic stresses (radiation, doxorubicin, cisplatin and hydrogen peroxide). In vitro experiments with primary endothelial cells have confirmed a specific microRNA is able to modulate endothelial function in response to genotoxic stress. Therefore, manipulating levels of this microRNA offers avenues to sensitize the endothelium to several DNA damaging agents or protect the endothelium from stress induced injury.
Patent Number: US9127284B2
Application Number: US13871716A
Inventor: Huang, Jian-dong | Yu, Bin | Yang, Mei | Shi, Lei
Priority Date: 4 May 2012
Priority Number: US9127284B2
Application Date: 26 Apr 2013
Publication Date: 8 Sep 2015
IPC Current: C12N000120 | A01N006300 | A61K003574 | A61K004800 | C12N000100 | C12N001500 | C12N001570 | C12N001574 | A61K003800 | A61K003900 | C12R000119
US Class: 1001
Assignee Applicant: The University of Hong Kong
Title: Modified bacteria and their uses thereof for the treatment of cancer or tumor
Usefulness: Modified bacteria and their uses thereof for the treatment of cancer or tumor
Summary: The method is useful for making modified facultative anaerobic gram-negative bacteria into an obligate anaerobe, which is useful for inhibiting and reducing the growth of a solid tumor cancer when administered in vivo, where the facultative anaerobic gram-negative bacteria are Salmonella sp. , preferably Salmonella typhi , Salmonella typhimurium , Salmonella choleraesuis and Salmonella enteritidis , Escherichia coli , Escherichia coli K-12 , Escherichia coli O157:H7, Shigella dysenteriae , Shigella flexneri , Shigella boydii , Shigella sonnei , Yersinia pestis , Yersinia pseudotuberculosis , and Yersina enterocolitica , and the solid tumor cancer is breast cancer, liver cancer, lung cancer, melanoma, colon carcinoma, kidney cancer, prostate cancer, neuroblastoma or bladder cancer (all claimed). Tests details are described but no results given.
Novelty: Making modified facultative anaerobic gram-negative bacteria into obligate anaerobe used to treat cancer, where facultative anaerobic bacteria comprise strictly hypoxia regulated essential gene expressing cassette
Disease Diagnostic/Treatment
Cancer/Tumor
9242000
State Of Development Gain and loss of function experiments with this miRNA demonstrates strong efficacy in, respectively, sensitizing endothelial cells to DNA damaging agents or protecting them from DNA damage. Specific target proteins of this miRNA that play a critical role in DNA maintenance in cells have been identified. Manipulation of these targets has shown the role of this pathway in modulating endothelial genotoxic stress response. In addition, intravenous delivery of this microrna mimic sensitizes tumor xenografts to radiation, decreases angiogenesis and tumor burden in a mouse model of colorectal cancer. Intellectual Property Info US rights available for licensure. Tech ID/UC Case 22955/2012-122-0 Related Cases 2012-122-0
USA
