title: Redirecting adenovirus tropism by genetic, chemical, and mechanical modification of the adenovirus surface for cancer gene therapy.
abstract: BACKGROUND
  Despite remarkable advancements, clinical evaluations of adenovirus (Ad)-mediated cancer gene therapies have highlighted the need for improved delivery and targeting.
  
  
  METHODS
  Genetic modification of Ad capsid proteins has been extensively attempted. Although genetic modification enhances the therapeutic potential of Ad, it is difficult to successfully incorporate extraneous moieties into the capsid and the engineering process is laborious. Recently, chemical modification of the Ad surface with nanomaterials and targeting moieties has been found to enhance Ad internalization into the target by both passive and active mechanisms. Alternatively, external stimulus-mediated targeting can result in selective accumulation of Ad in the tumor and prevent dissemination of Ad into surrounding nontarget tissues. In the present review, we discuss various genetic, chemical, and mechanical engineering strategies for overcoming the challenges that hinder the therapeutic efficacy of Ad-based approaches.
  
  
  CONCLUSIONS
  Surface modification of Ad by genetic, chemical, or mechanical engineering strategies enables Ad to overcome the shortcomings of conventional Ad and enhances delivery efficiency through distinct and unique mechanisms that unmodified Ad cannot mimic. However, although the therapeutic potential of Ad-mediated gene therapy has been enhanced by various surface modification strategies, each strategy still possesses innate limitations that must be addressed, requiring innovative ideas and designs.
authors.affiliation: a Department of Bioengineering, College of Engineering , Hanyang University , Seoul , Korea.
authors.forename: A-Rum
authors.initials: AR
authors.lastname: Yoon
authors.affiliation: a Department of Bioengineering, College of Engineering , Hanyang University , Seoul , Korea.
authors.forename: Jinwoo
authors.initials: J
authors.lastname: Hong
authors.affiliation: a Department of Bioengineering, College of Engineering , Hanyang University , Seoul , Korea.|b Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry , University of Utah , Salt Lake City , UT , USA.
authors.forename: Sung Wan
authors.initials: SW
authors.lastname: Kim
authors.affiliation: a Department of Bioengineering, College of Engineering , Hanyang University , Seoul , Korea.
authors.forename: Chae-Ok
authors.initials: CO
authors.lastname: Yun
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D018523:Tropism
keywords: Adenovirus; active targeting; chimeric fiber; enhanced permeability and retention effect; external stimuli-induced targeting; fiber modification; minor capsid protein; nanomaterial; oncolytic adenovirus; passive targeting; polymer; targeting moiety; tumor microenvironment-responsive delivery