| Autor: |
Chidiebere U. Awah, Yana Glemaud, Fayola Levine, Kiseok Yang, Afrin Ansary, Fu Dong, Leonard Ash, Junfei Zhang, Olorunseun O. Ogunwobi |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Frontiers in Genetics, Vol 14 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1664-8021 |
| DOI: |
10.3389/fgene.2023.1184600 |
| Popis: |
Breast, lung, and colorectal cancer resistance to molecular targeted therapy is a major challenge that unfavorably impacts clinical outcomes leading to hundreds of thousands of deaths annually. In ERBB2+ cancers regardless of the tissue of origin, many ERBB2+ cancers are resistant to ERBB2-targeted therapy. We discovered that ERBB2+ cancer cells are enriched with poly U sequences on their 3’UTR which are mRNA-stabilizing sequences. We developed a novel technology, in which we engineered these ERBB2 mRNA-stabilizing sequences to unstable forms that successfully overwrote and outcompeted the endogenous ERBB2 mRNA-encoded message and degraded ERBB2 transcripts which led to the loss of the protein across multiple cancer cell types both in the wildtype and drug-resistance settings in vitro and in vivo, offering a unique safe novel modality to control ERBB2 mRNA and other pervasive oncogenic signals where current targeted therapies fail. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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