Advantage and Core Benefit
- Tumor-Selective Cell Death Induction: C11orf97 was identified as a binding partner of ferrichrome, an antitumor peptide that selectively induces cell death in cancer cells. It holds strong potential as a cancer-specific therapeutic target.
- Low Toxicity and High Selectivity: Ferrichrome shows no toxicity even at high doses, and no significant abnormalities have been reported in C11orf97 knockout mice, indicating C11orf97 is a highly selective and safe therapeutic target.
- siRNA-Mediated Antitumor Effect: Knockdown of C11orf97 via siRNA has demonstrated significant tumor suppression in vitro and in mouse xenograft models.
Background and Technology
Ferrichrome is a bacterial siderophore (metal-chelating compound) that selectively induces cell death in colorectal, gastric, pancreatic, and esophageal cancer cells. Preclinical toxicity studies in mice have shown that repeated administration at four times the therapeutic dose for two weeks, or a single administration at 60 times the dose, caused no toxicity. Normal cells were also unaffected, suggesting that ferrichrome and its molecular target may offer a low-toxicity cancer treatment strategy.
To identify the target of ferrichrome, a CRISPR library screening was conducted, leading to the discovery of C11orf97, a previously uncharacterized gene. Direct binding between ferrichrome and C11orf97 protein was confirmed. Furthermore, siRNA-mediated knockdown of C11orf97 significantly suppressed the growth of various cancer cell lines without affecting normal cells. In mouse xenograft models, siRNA targeting C11orf97 showed clear tumor-suppressive effects.
These results highlight C11orf97 as a core mediator of ferrichrome’s antitumor activity and a promising cancer-specific target with high selectivity and safety. It has broad potential for drug development across various modalities, including nucleic acid therapeutics, small molecules, and PROTACs.
Data
- CRISPR Screening: C11orf97 was identified through a CRISPR library screen as a key mediator of ferrichrome’s antitumor effect.
- siRNA-Based Antitumor Effect: siRNA targeting C11orf97 demonstrated significant tumor volume reduction in a mouse xenograft model (see figure).
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Patent & Publication
Patent pending (C11orf97-related; unpublished), JP Patent No. 6830255 (Ferrichrome; granted)
Publications: Konishi H, Nat Commun. 2016; Kita A, Int J Oncol. 2020
Researcher
Dr. Hiroaki Konishi (Asahikawa Medical University)
Expectations
We welcome collaborative research and licensing opportunities with pharmaceutical and biotech companies interested in developing nucleic acid therapeutics, PROTACs, or other novel modalities targeting C11orf97. Unpublished data can be disclosed under a confidentiality agreement with Asahikawa Medical University. Direct meetings with the lead researcher can also be arranged upon request.
Project ID:WL-05281