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Kyushu University Hospital Kyushu University Hospital
16
Kyushu University Hospital Kyushu University Hospital
Development of nucleic acid medicine targeting angiogenic factor: YB-1 for treatment of refractory cancer and proliferative vascular diseases
■ SynopsisA new nucleic acid sequence that effectively inhibits Y-box binding preotein-1 (YB-1) expression
and angiogenesis was identified. This sequence could significantly inhibit the vascular growth/ tube
formation and enables the induction of apoptosis in tumor vascular endothelium (patent applied
for). In this project, we would develop a delivery device for the anti-YB-1 nucleic acid, or modulate
the structure of anti-YB-1 nucleic acid to function in the living body without a delivery device. The
resultant outcome will open a way for new therapeutic approaches to treat refractory cancer and
pathologically proliferative vascular diseases.
Innovation Center for Medical Redox Navigation, Kyushu University
Related keywords:angiogenic factor YB-1, nucleic acid medicine, delivery device, refractory cancer, pathologically proliferative vascular diseases
Intellectual property information:Patent pending
Target diseases: refractory cancer, pathologically proliferative vascular lesions
αα1
αα1
pYB-1
YB-1
pYB-1
AKT
Characteristics of seeds*Nucleic acid sequence newly identified for inhibiting YB-1 expression suppresses the vascular growth and tube formation more significantly than the reported RNA interference sequences, and by itself can induce apoptosis in tumor vascular endothelium (patent applied for), resulting in the decrease in microvascular density (MVD) in tumor tissues (see the right figure).
*Because YB-1 is specifically overexpressed in tumor vessels (see the bottom figure right) and the incorporation of the delivery device is accumulated into tumor tissues by enhanced permeability and retention (EPR) effect, the anti-YB-1 nucleic acid seems to have some advantages over conventional angiogenesis inhibitors (Avastin and VEGFR kinase inhibitors) that potentially influence on normal vessels (see the bottom figure left).
Anti-VEGF antibody
Inflammatory tissuesCancer tissues
Normal tissues
<No inhibitory effect>
<Frequent expression specifically in the tumor vessel>
Y B - 1 i n h i b i t i n g nucleic acid medicine
Involvement in the traits of the tumor vesselInvolvement in the traits of the tumor vessel
Target gene
VEGFR kinase inhibitors(cediranib; tivozanib)
<Inhibit ion of normal vascular functions>