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Critical Reviews™ in Therapeutic Drug Carrier Systems
Facteur d'impact: 2.9 Facteur d'impact sur 5 ans: 3.72 SJR: 0.573 SNIP: 0.551 CiteScore™: 2.43

ISSN Imprimer: 0743-4863
ISSN En ligne: 2162-660X

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Critical Reviews™ in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.v23.i2.10
pages 89-110

Role of Immunostimulatory DNA and TLR9 in Gene Therapy

Kei Yasuda
Renal Section, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
Hermann Wagner
Institute of Medical Microbiology, Immunology, and Hygiene, Technical University of Munich, Munich, Germany
Yoshinobu Takakura
Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan


One of the key issues of DNA-based therapies is the immunostimulatory effect caused by DNA, which it has a significant impact on the consequences of these therapies. This is a result of the recognition by Toll-like receptor-9 (TLR9); a pattern recognition receptor for unmethylated CpG motifs within DNA sequences. However, recent studies show that TLR9 can recognize non-CpG motifs and induce cellular activation when DNA is efficiently delivered to TLR9, for example, by cationic lipids. Moreover, recent research shows that TLR9−independent immunoactivation could take place. Here, we have attempted to present an overview of immunoactivation by DNA to optimize DNA-based therapies.

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