fulltext.study @t Gmail

A targeted adenovirus vector displaying a human fibronectin type III domain-based monobody in a fiber protein

Paper ID Volume ID Publish Year Pages File Format Full-Text
6170 466 2013 11 PDF Available
Title
A targeted adenovirus vector displaying a human fibronectin type III domain-based monobody in a fiber protein
Abstract

A major drawback of adenovirus (Ad) vectors is their nonspecific transduction into various types of cells or tissue after in vivo application, which might lead to unexpected toxicity and tissue damage. To overcome this problem, we developed a fiber-mutant Ad vector displaying a monobody specific for epidermal growth factor receptor (EGFR) or vascular endothelial growth factor receptor 2 (VEGFR2) in the C-terminus of the knobless fiber protein derived from T4 phage fibritin. A monobody, which is a single domain antibody mimic based on the tenth human fibronectin type III domain scaffold with a structure similar to the variable domains of antibodies, would be suitable as a targeting molecule for display on the Ad capsid proteins because of its highly stable structure even under reducing conditions and low molecular weight (approximately 10 kDa). Surface plasmon resonance (SPR) analysis revealed that the monobody-displaying Ad vector specifically bound to the targeted molecules, leading to significant increases in cellular binding and transduction efficiencies in the targeted cells. Transduction with the monobody-displaying Ad vectors was significantly inhibited in the presence of the Fc-chimera protein of EGFR and VEGFR2. This monobody-displaying Ad vector would be a crucial resource for targeted gene therapy.

Keywords
Adenovirus vector; Monobody; Knobless fiber; Targeted gene delivery; EGFR; VEGFR2
First Page Preview
A targeted adenovirus vector displaying a human fibronectin type III domain-based monobody in a fiber protein
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 16, May 2013, Pages 4191–4201
Authors
, , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering