Background / Context / Abstract:

Abstract:

– Two independent antisense oligonucleotides (ASOs) targeting GREB1 and Arl4c gene.
– GREB1 was identified as one of the important factors controlling a cell proliferation and as a therapeutic target of hepatoblastoma.
– Arl4c overexpressed in hepatocellular carcinoma tumors and colorectal cancer liver metastases, and was detected as a key factor for motility, invasion and proliferation of the cancer cells.

Background:

Researchers focus on comprehensively understanding the molecular mechanisms of the Wnt signalling regulated with other pathway, such as TGF-β, EGF, and Hedgehog signalling.
Hepatoblastoma (HB) is a rare form of liver cancer, affecting just a few individuals per million, it is the leading cause of liver cancer in infants and young children. Researchers realized that a large number of HB patients — up to 90% in some cases — expressed Growth Regulating Estrogen Receptor Binding 1 (GREB1) in the nucleus of tumor lesions. Additionally, researchers revealed the molecular mechanisms which Wnt signalling abnormal activation promotes HB growth with GREB1 expression.
According to Researches, ADP-ribosylation factor-like 4c (Arl4c) was identified as a small molecule GTP-binding protein, which is expressed by Wnt and EGF signalling, plays an important role in tubulogenesis of cultured cells and the ureters. Arl4c is highly expressed in hepatocellular carcinoma (HCC), lung cancer, and colorectal cancer.

Technology Overview:

Researchers investigated the suppressing tumor formation effect and inhibiting growth effect in vivo study using GREB1- and Arl4c-targeted AmNA-modified ASOs (*) injected by i.p.
* AmNA-modified ASO: In these projects, Amido-bridged nucleic acid (AmNA) was used to Improve nuclease resistance and decrease hepatotoxicity.

Benefits:

Advantages

– GREB1- or Arl4c-targeted ASOs successfully decreased and suppressed the tumors growth.

Potential Applications / Potential Markets:

Antisense oligonucleotides (ASOs) drugs

State of Development / Opportunity / Seeking:

・Available for exclusive and non-exclusive licensing
・Exclusive/non-exclusive evaluation for defined period (set up for options)
・Collaborative/supportive research

※Seeking
1. Development partner
2. Licensing　

IP Status:

1. National phase  US, JP
2. National phase EP, US, JP

Contact: