| Literature DB >> 31048459 |
Hokyung K Chung1,2,3, Xinzhi Zou4, Bryce T Bajar3,4, Veronica R Brand3,4, Yunwen Huo2,3,4, Javier F Alcudia5, James E Ferrell6, Michael Z Lin7,3,4,6.
Abstract
An important goal in synthetic biology is to engineer biochemical pathways to address unsolved biomedical problems. One long-standing problem in molecular medicine is the specific identification and ablation of cancer cells. Here, we describe a method, named Rewiring of Aberrant Signaling to Effector Release (RASER), in which oncogenic ErbB receptor activity, instead of being targeted for inhibition as in existing treatments, is co-opted to trigger therapeutic programs. RASER integrates ErbB activity to specifically link oncogenic states to the execution of desired outputs. A complete mathematical model of RASER and modularity in design enable rational optimization and output programming. Using RASER, we induced apoptosis and CRISPR-Cas9-mediated transcription of endogenous genes specifically in ErbB-hyperactive cancer cells. Delivery of apoptotic RASER by adeno-associated virus selectively ablated ErbB-hyperactive cancer cells while sparing ErbB-normal cells. RASER thus provides a new strategy for oncogene-specific cancer detection and treatment.Entities:
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Year: 2019 PMID： 31048459 PMCID： PMC7053279 DOI： 10.1126/science.aat6982
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728