title: An adenovirus vector incorporating carbohydrate binding domains utilizes glycans for gene transfer.
abstract: BACKGROUND
  Vectors based on human adenovirus serotype 5 (HAdV-5) continue to show promise as delivery vehicles for cancer gene therapy. Nevertheless, it has become clear that therapeutic benefit is directly linked to tumor-specific vector localization, highlighting the need for tumor-targeted gene delivery. Aberrant glycosylation of cell surface glycoproteins and glycolipids is a central feature of malignant transformation, and tumor-associated glycoforms are recognized as cancer biomarkers. On this basis, we hypothesized that cancer-specific cell-surface glycans could be the basis of a novel paradigm in HAdV-5-based vector targeting.
  
  
  RESULTS
  As a first step toward this goal, we constructed a novel HAdV-5 vector encoding a unique chimeric fiber protein that contains the tandem carbohydrate binding domains of the fiber protein of the NADC-1 strain of porcine adenovirus type 4 (PAdV-4). This glycan-targeted vector displays augmented CAR-independent gene transfer in cells with low CAR expression. Further, we show that gene transfer is markedly decreased in cells with genetic glycosylation defects and by inhibitors of glycosylation in normal cells.
  
  
  CONCLUSIONS
  These data provide the initial proof-of-concept for HAdV-5 vector-mediated gene delivery based on the presence of cell-surface carbohydrates. Further development of this new targeting paradigm could provide targeted gene delivery based on vector recognition of disease-specific glycan biomarkers.
authors: Cancer Biology Division, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States of America.
authors: Julius W
authors: JW
authors: Kim
authors: Joel N
authors: JN
authors: Glasgow
authors: Masaharu
authors: M
authors: Nakayama
authors: Ferhat
authors: F
authors: Ak
authors: Hideyo
authors: H
authors: Ugai
authors: David T
authors: DT
authors: Curiel
mesh_terms: D000260:Adenoviruses, Human; D025662:Adenoviruses, Porcine / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D017931:DNA Primers / Q000235:genetics; D018390:Gene Targeting / Q000379:methods*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D011134:Polysaccharides / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D011134:Polysaccharides
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