Publikationsdatenbank

Expression of an engineered soluble coxsackievirus and adenovirus receptor by a dimeric AAV9 vector inhibits adenovirus infection in mice (2015)

Art

Poster

Autoren

Roger, C.

Pozzuto, T.

Klopfleisch, R. (WE 12)

Kurreck, J.

Fechner, H.

Pinkert, S.

Kongress

Collaborative Congress of the European­ Society­ of ­Gene­ & Cell­ Therapy (ESGCT) and Finnish­ Society ­of­ Gene­ Therapy (FSGT)

Helsinki, Finnland, 17. – 20.09.2015

Quelle

Gene therapy

Bandzählung: 22

Heftzählung: 6

Seiten: 458 – 466

ISSN: 0969-7128

Sprache

Englisch

Verweise

URL (Volltext): http://www.nature.com/doifinder/10.1038/gt.2015.19

DOI: 10.1038/gt.2015.19

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Immunosuppressed (IS) patients, such as recipients of hematopoietic stem cell transplantation, occasionally develop severe and fatal adenovirus (Ad) infections. Here, we analyzed the potential of a virus receptor trap based on a soluble coxsackievirus and Ad receptor (sCAR) for inhibition of Ad infection. In vitro, a dimeric fusion protein, sCAR-Fc, consisting of the extracellular domain of CAR and the Fc portion of human IgG1 and a monomeric sCAR lacking the Fc domain, were expressed in cell culture. More sCAR was secreted into the cell culture supernatant than sCAR-Fc, but it had lower Ad neutralization activity than sCAR-Fc. Further investigations showed that sCAR-Fc reduced the Ad infection by a 100-fold and Ad-induced cytotoxicity by ~20-fold. Not only was Ad infection inhibited by sCAR-Fc applied prior to infection, it also inhibited infection when used to treat ongoing Ad infection. In vivo, sCAR-Fc was delivered to IS mice by an AAV9 vector, resulting in persistent and high (>40 μg ml−1) sCAR-Fc serum levels. The sCAR-Fc serum concentration was sufficient to significantly inhibit hepatic and cardiac wild-type Ad5 infection. Treatment with sCAR-Fc did not induce side effects. Thus, sCAR-Fc virus receptor trap may be a promising novel therapeutic for treatment of Ad infections.