The standard adenovirus vector, Ad5, is an important vector because it can infect a variety of non-dividing cells and elicit high levels of transgene expression. Unfortunately, we and others have recently shown that Ad5 poorly transduces a number of human cells and tissues, mainly because they lack the Coxsackie adenovirus receptor (CAR). Particularly, important cells that are inefficiently transduced by Ad5 vectors are hematopoietic cells and primitive stem cells. A new adenovirus vector has been developed where the fiber gene from adenovirus type 35 has been substituted for the Ad5 fiber. Ad35 fiber does not bind CAR and enters the cell by a different mechanism. In tabular form below we present tissues that have been shown to be efficiently infected by Ad5F35 vectors, but not Ad5 vectors. These have been shown to have a higher transduction efficiency in most human cells than their Ad5 counterparts.
Hematopoietic cells: Shayakhmetov DM, Papayannopoulou T, Stamatoyannopoulos G, and Lieber A. Efficient Gene Transfer into Human CD34 (+) Cells by a Retargeted Adenovirus Vector. J Virol 2000; 74: 2567-2583
Primitive hematopoietic stem cells: Yotnda P, Onishi H, Heslop HE, Shayakhmetov D, Lieber A, Brenner M, and Davis A. Efficient Infection of Primitive Hematopoietic Stem Cells by Modified Adenovirus. Gene Ther 2001; 8: 930-37.
Human skin fibroblasts: Unpublished
Several human tumors including bladder and pancreas: Unpublished
MRC-5 cells: Unpublished