Targeting EGFR/HER2/HER3 with a Three-in-One Aptamer-siRNA Chimera Confers Superior Activity against HER2⁺ Breast Cancer.

ABSTRACT: HER family members are interdependent and functionally compensatory. Simultaneously targeting EGFR/HER2/HER3 by antibody combinations has demonstrated superior treatment efficacy over targeting one HER receptor. However, antibody combinations have their limitations, with high immunogenicity and high cost. In this study, we have developed a three-in-one nucleic acid aptamer-small interfering RNA (siRNA) chimera, which targets EGFR/HER2/HER3 in one molecule. This inhibitory molecule was constructed such that a single EGFR siRNA is positioned between the HER2 and HER3 aptamers to create a HER2 aptamer-EGFR siRNA-HER3 aptamer chimera (H2EH3). EGFR siRNA was delivered into HER2-expressing cells by HER2/HER3 aptamer-induced internalization. HER2/HER3 aptamers act as antagonist molecules for bloc

SUBMITTER: Yu X 

PROVIDER: S-EPMC5862534 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature