Advanced Molecular Therapy
We are developing a therapy targeting specific splicing variants
- Comparison of the functions of pathologic variant and physiological splicing variant of periostin
- Analysis of pathologic conditions of chronic inflammatory diseases and pathologic periostin in blood
- Comprehensive analysis of conjugated proteins of pathologic periostin variant
- Transport of periostin variant via exosomes
- Inhibitory effect of exon skipping on pathologic periostin variant
Analysis of mechanism of chronic inflammatory diseases through splicing variant
“Alternative splicing variant (ASV),” a mechanism in which multiple products are produced from a single gene by variant switch, not only enables the acquisition of complex morphology and cellular functions of multicellular organisms but is also deeply involved in the pathogenesis of several diseases.
The purpose of this research is to selectively inhibit only ASV that is involved in the pathogenesis of chronic diseases such as cancer, heart failure, arteriosclerosis, renal failure, and diabetic retinopathy without inhibiting physiological ASV. We think that a safe and efficient therapy can be provided by selective inhibition of ASV.
Genes express splicing variants in pathological conditions such as acute myocardial infarction, diabetic retinopathy, inflammatory bowel disease, arteriosclerosis, aneurysm, asthma, cancer, and renal failure, and we have confirmed that inhibiting specific splicing variants improves such pathological conditions. First, we will analyze chemotherapy-resistant triple negative breast cancer (TNBC).
Triple negative breast cancer is a type of cancer in which estrogen receptor is negative, progesterone receptor is negative, and HER2, the growth factor receptor, is negative and cannot be treated with targeted therapy. Quite a few of them are resistant to chemotherapy. Since there is no therapy, it is a significant cause of death in women of the AYA generation and it is a disease with high unmet needs worldwide.
Chemotherapy-resistant TNBC was successfully treated in the animal experiment by inhibiting this specific variant and we are planning to create and apply a human neutralizing antibody clinically in the future. We expect that the success in this research will save many women suffering TNBC worldwide.
In our course, we will analyze the mechanism of pathogenesis of pathologic periostin and the in vivo function such as transport of periostin variant via exosomes.
