Conformation-dependent binding and tumor-targeted delivery of siRNA by a designed TRBP2: Affibody fusion protein

Publication date: Available online 23 February 2015 Source:Nanomedicine: Nanotechnology, Biology and Medicine Author(s): Ghulam Hassan Dar , Vijaya Gopal , Madhusudhana Rao Efficiency of systemically delivered siRNA in gene silencing is compromised due to lack of target-specific delivery and rapid clearance of siRNA by in vivo elimination pathways. We designed a fusion protein consisting of a dsRNA binding domain of Transactivation Response RNA Binding Protein (TRBP2) fused to ErbB2 binding affibody (AF) for target specific delivery of siRNA. Designated as TRAF, the fusion protein is stable and binds efficiently and specifically to siRNA, forming homogenous non-aggregated and nuclease-resistant particles that efficiently and selectively transport siRNA into HER-2 overexpressing cancer cells and tissues. Administration of siRNA by TRAF into cells resulted in significant silencing of chosen genes involved in cell proliferation viz. AURKB and ErbB2 . Noticeably, intravenous administration of TRAF: siRNA against these genes resulted in remarkable tumor suppression in the SK-OV-3 xenograft mouse model. Our results establish the potential of engineered proteins for specific and systemic delivery of siRNA for cancer therapy. Graphical abstract
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research