Ad5F35 Vectors - Vector Development Laboratory

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Ad5/F35 Vectors

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.

Tissue	Reference
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.
Mesenchymal stem cells	Olmsted-Davis EA, Gugala Z, Gannon FH, Yotnda P, McAlhany RE, Lindsey RW, Davis AR. Use of a Chimeric Adenovirus Vector Enhances BMP2 Production and Bone Formation. Hum Gene Ther 2002;13(11):1337-47.
Human skin fibroblasts	Unpublished
Several human tumors including bladder and pancreas	Unpublished
MRC-5 cells	Unpublished

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