Oncomir expression directed targeted chemotherapy
MicroRNAs (miRNAs) are an abundant class of short endogenous noncoding RNAs that act as post-transcriptional regulators of gene expression by base-pairing with their target mRNAs. To date, several hundred miRNAs have been described in humans and a large number of them have been implicated in the development and progression of cancer. miRNAs that have been experimentally shown to directly induce tumor phenotypes (i.e., formation) have been termed "oncomirs".
In this invention we utilize this differential expression of a known oncomir to selectively target cancer cells. Selected targeting is achieved by differentially expressing a "killer gene" in the cancerous cells, by expressing it under the control of the oncomir promoter. Such “killer gene” could be a toxin (such as the diphtheria toxin-A), the viral tymidine kinase gene, or an apoptosis inducing genes, all of these genes were previously shown to be efficient in destruction of cancer cells.
The specific oncomir was shown to target multiple tumor/metastasis suppressor genes and to have a role in tumor growth, invasion and metastasis. Numerous studies show that this oncomir is exclusively expressed in cancerous cell lines and solid human tumors, but not in non-transformed cell lines or in the adjacent non cancerous tissue.
A novel and promising approach targeting an amazingly broad range of cancer types.
Cancer, which is the cause of about 13% of all deaths worldwide, may affect people at all ages, even fetuses, but the risk for most varieties increases with age. Nearly all cancers are caused by abnormalities in the genetic material of the transformed cells. There are over 200 different types of cancer, and therefore different cancers can be considered to be different diseases. However, at a molecular and cellular level all cancers share common mechanisms that result in uncontrolled cell division.
Selective targeting of a specific cancer type using differentially expressed genes has been previously successfully demonstrated where regulatory sequences of the H19 gene differentially expressed in bladder cancer were used to control the expression of the diphtheria toxin. However this strategy is limited to a specific cancer type. The specific oncomiR utilized in this invention could efficiently target an amazingly broad range of cancer types. Currently there are no known drugs that have the potential of targeting such a broad range of different cancers types.
While various applications using miRNAs to control tissue tropism have been published, selective targeting cancer cells using miRNAs targeting such a broad range of cancers has never been attempted. Thus we propose a novel and promising approach that could efficiently target an amazingly broad range of cancer types.