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J. Biol. Chem., Vol. 279, Issue 46, 48410-48419, November 12, 2004

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A DNA Aptamer Prevents Influenza Infection by Blocking the Receptor Binding Region of the Viral Hemagglutinin^*

Sung Ho Jeon, Basak Kayhan, Tamar Ben-Yedidia, and Ruth Arnon¶

From the Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel

Influenza A virus infection is a major source of morbidity and mortality worldwide. Current means of control for influenza are based on prophylaxis by vaccines and on treatment by the available specific influenza neuraminidase inhibitor drugs. The approach taken in the present study is to prevent and/or ameliorate influenza infection by site-specific blocking of the viral binding to host cell receptors. We describe a novel oligonucleotide, known also as an aptamer, which has been designed to complement the receptor-binding region of the influenza hemagglutinin molecule. It was constructed by screening a DNA library and processing by the selective evolution of ligands by exponential enrichment (SELEX) procedure. We show that this DNA aptamer is indeed capable of inhibiting the hemagglutinin capacity of the virus, as well as in the prevention of viral infectivity in vitro, in tissue culture. Furthermore, it inhibits viral infection by different influenza strains in an animal model, as manifested by 90-99% reduction of virus burden in the lungs of treated mice. The mode of action of this aptamer is by blocking the binding of influenza virus to target cell receptors and consequently prevention of the virus invasion into the host cells.

Received for publication, August 9, 2004 , and in revised form, September 8, 2004.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea.

^¶ To whom all correspondence should be addressed. Tel.: 972-8-9344017; Fax: 972-8-9469712; E-mail: ruth.arnon{at}weizmann.ac.il.

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