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The present study focused on effectively reducing viral protein levels.We designed siRNAs (HBV-siRNA) that target consensus sequences in HBV genomes. To prevent the emergence of escaped mutant virus, we mixed three HBV-siRNAs (HBV-siRNAmix); the mixture was encapsulated in a novel pH-sensitive multifunctional envelope-type nanodevice (MEND), a hepatocyte-specific drug delivery system. Coagulation factor 7 siRNA was used to assess delivery and knockdown efficiencies of MEND/siRNA treatments in mice. The potency of MEND/HBV-siRNAmix was evaluated in primary human hepatocytes and in chimeric mice with humanized liver persistently infected with HBV.Effective knockdown of targets, efficient delivery of siRNA, and liver-specific delivery were each observed with MEND. MEND/HBV-siRNA caused efficient reduction of HBsAg and HBeAg in vitro and in vivo. However, ETV treatment did not efficiently reduce HBsAg or HBeAg when compared with a single MEND/HBV-siRNAmix treatment. Furthermore, the suppressive effects of a single dose of MEND/HBV-siRNAmix persisted for 14days in vitro and in vivo.We demonstrated that MEND/HBV-siRNA controlled HBV more efficiently than did ETV. Furthermore, the effect of a single dose of MEND/HBV-siRNA persisted for a long time. These results indicated that MEND/HBV-siRNA may be a promising novel HBV treatment that is more effective than reverse transcriptase inhibitors."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1420282801205285376","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"10547780"},{"@type":"NRID","@value":"1000010547780"},{"@type":"NRID","@value":"9000240114582"},{"@type":"NRID","@value":"9000019012266"},{"@type":"NRID","@value":"9000237783354"},{"@type":"NRID","@value":"9000242544760"},{"@type":"NRID","@value":"9000018532369"},{"@type":"NRID","@value":"9000020825725"},{"@type":"NRID","@value":"9000239881405"},{"@type":"NRID","@value":"9000240022957"},{"@type":"NRID","@value":"9000237782719"},{"@type":"NRID","@value":"9000024427095"},{"@type":"NRID","@value":"9000340953622"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/yamamoto-nk"}],"foaf:name":[{"@value":"Naoki 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