Efficient gene transfer and expression in islets by an adenoviral vector that lacks all viral genes.

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

Efficient gene transfer and expression in islets by an adenoviral vector that lacks all viral genes.

Cell Transplant. 1999 Nov-Dec;8(6):661-71. Unique Identifier : AIDSLINE MED/20163430
Guo Z; Shen J; Mital D; Hong Y; Alemany R; Zhong WW; Jensik SC; Williams JW; Department of General Surgery, Rush-Presbyterian-St. Lukes's; Medical Center, Chicago, IL 60612, USA. zhiguang@tc.umn.edu

Abstract: Although adenoviral vector-mediated gene transfer has significant potential for gene therapy, host immune responses to virally expressed proteins and small insert capacity may limit its clinical application. In order to overcome these disadvantages, a new adenoviral vector that lacks all viral genes has been developed. Using the green fluorescent (GFP) gene as a reporter gene, we investigated the efficiency of gene transfer by this all-viral-genes-deleted and minimal cis-element remaining adenoviral vector (miniAd-GFP) in islets in vitro and ex vivo, and compared it with the E1-deleted adenoviral vector (E1-GFP). One day after in vitro infection, GFP was expressed in both miniAd-GFP- and E1-GFP-infected islets. The percentage of GFP-positive single cells was not significantly different between miniAd-GFP-infected islets and E1-GFP-infected islets. When these islets were transplanted into syngeneic diabetic mice, both miniAd-GFP- and E1-GFP-infected islet grafts reversed diabetes, and normal blood glucose levels were maintained for over 20 weeks posttransplantation. Mild lymphocyte infiltration was found in all E1-GFP-infected islet grafts at all time points. However, this was not seen in most miniAd-GFP-infected islet grafts. Our results indicate that gene transfer by an adenoviral vector that lacks all viral genes is as efficient as E1-deleted adenoviral vector-mediated gene transfer in islets. Furthermore, this adenoviral vector might be less immunogeneic than the E1-deleted adenoviral vector.

Keywords: JOURNAL ARTICLE Adenoviridae/*GENETICS Animal CD4-Positive T-Lymphocytes/IMMUNOLOGY CD8-Positive T-Lymphocytes/IMMUNOLOGY Diabetes Mellitus, Experimental/IMMUNOLOGY/PHYSIOPATHOLOGY/ SURGERY Gene Expression *Gene Transfer Genes, Reporter Genes, Viral *Genetic Vectors Insulin/METABOLISM *Islets of Langerhans Transplantation/IMMUNOLOGY/PHYSIOLOGY Luminescent Proteins/GENETICS Mice Mice, Inbred BALB C Support, Non-U.S. Gov't Transplantation, Isogeneic

000630
A0061974

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