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>