adenovirus vector-derived va-rna-mediated innate immune responses腺病毒vector-derived va-rna-mediated先天免疫反应.pdfVIP

Pharmaceutics 2011, 3, 338-353; doi:10.3390/pharmaceutics3030338 OPEN ACCESS pharmaceutics ISSN 1999-4923 /journal/pharmaceutics Review Adenovirus Vector-Derived VA-RNA-Mediated Innate Immune Responses Mitsuhiro Machitani 1, Tomoko Yamaguchi 2, Kahori Shimizu 1, Fuminori Sakurai 1, Kazufumi Katayama 1, Kenji Kawabata 2,3 and Hiroyuki Mizuguchi 1,2,4,* 1 Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamadaoka, Suita, Osaka, 565-0871, Japan 2 Laboratory of Stem Cell Regulation, National Institute of Biomedical Innovation (NiBio), Osaka, 567-0085, Japan 3 Laboratory of Biomedical Innovation, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamadaoka, Suita, Osaka, 565-0871, Japan 4 The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6, Yamadaoka, Suita, Osaka, 565-0871, Japan * Author to whom correspondence should be addressed; E-Mail: mizuguch@phs.osaka-u.ac.jp; Tel.: +81-6-6879-8185; Fax: +81-6-6879-8186. Received: 19 May 2011; in revised form: 27 June 2011 / Accepted: 5 July 2011 / Published: 11 July 2011 Abstract: The major limitation of the clinical use of replication-incompetent adenovirus (Ad) vectors is the interference by innate immune responses, including induction of inflammatory cytokines and interferons (IFN), following in vivo application of Ad vectors. Ad vector-induced production of inflammatory cytokines and IFNs also results in severe organ damage and efficient ind