Transplacental delivery of factor IX Fc-fusion protein ameliorates bleeding phenotype of newborn hemophilia B mice

Sakurai, Fuminori; Iizuka, Shunsuke; Tsukamoto, Tomohito; Shiota, Aoi; Shimizu, Kahori; Ohashi, Kazuo; Mizuguchi, Hiroyuki

doi:https://doi.org/10.1016/j.jconrel.2024.08.022

Transplacental delivery of factor IX Fc-fusion protein ameliorates bleeding phenotype of newborn hemophilia B mice

Sakurai, Fuminori; Iizuka, Shunsuke; Tsukamoto, Tomohito et al.

Journal of Controlled Release, 2024, 374, 415-424

アクセス数:687件（2025-07-08 23:45 集計）

固定URL: https://hdl.handle.net/11094/98331

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タイトル	Transplacental delivery of factor IX Fc-fusion protein ameliorates bleeding phenotype of newborn hemophilia B mice
著者	NRID 1000070370939 1000070370939 researchmap permalink read0165081 read0165081 Scopus Author ID 7003748169 7003748169 著者名 Sakurai, Fuminori
	著者名 Iizuka, Shunsuke
	NRID 1000020977342 1000020977342 researchmap permalink tsukamoto-t tsukamoto-t 著者名 Tsukamoto, Tomohito
	著者名 Shiota, Aoi
	NRID 1000050737749 1000050737749 ORCID 0000-0003-1574-5526 0000-0003-1574-5526 researchmap permalink kahorishimizu kahorishimizu 著者名 Shimizu, Kahori
	NRID 1000040364062 1000040364062 著者名 Ohashi, Kazuo
	NRID 1000050311387 1000050311387 researchmap permalink read0165079 read0165079 Scopus Author ID 57195381326 57195381326 著者名 Mizuguchi, Hiroyuki
キーワード等	Adenovirus vector
	Factor IX
	Hemophilia
	Transplacental delivery
内容	Sakurai F., Iizuka S., Tsukamoto T., et al. Transplacental delivery of factor IX Fc-fusion protein ameliorates bleeding phenotype of newborn hemophilia B mice. Journal of Controlled Release 374, 415 (2024); https://doi.org/10.1016/j.jconrel.2024.08.022.
抄録	Hemophilia B is an inherited hemorrhagic disorder characterized by a deficiency of blood coagulation factor IX (FIX) that results in abnormal blood coagulation. The blood coagulation is already evident in hemophiliacs at the fetal stage, and thus intracranial hemorrhage and other bleeding complications can occur at birth, leading to sequelae. Therefore, it is important to develop effective treatments for hemophiliacs in utero. In this study, in order to transplacentally deliver FIX from pregnant mice to their fetuses, an improved adenovirus (Ad) vector expressing human FIX fused with the IgG Fc domain (FIX Fc fusion protein), which plays a crucial role in neonatal Fc receptor (FcRn)-mediated transcytosis across the placenta, was intravenously administered to E13.5 pregnant mice. Significant levels of FIX Fc fusion protein were detected in 0-day-old newborn mice whose mothers were administered an Ad vector expressing FIX Fc fusion protein. Wild-type FIX overexpressed in the pregnant mice was not delivered to the fetuses. Plasma FIX levels in the newborn mice were relatively well correlated with those in their mothers, although transplacental delivery efficiencies of FIX Fc fusion protein were slightly reduced when the FIX Fc fusion protein was highly expressed in the mother mice. Plasma FIX levels in the newborn mice were about 3.6–6.4% of those in their mothers, Transplacental delivery of FIX Fc fusion protein to their fetuses successfully improved the blood clotting ability in the newborn mice.
出版者	Elsevier B.V.
収録物名	Journal of Controlled Release
巻(号)	374
ページ	415-424
刊行年月	2024-10-01
言語	英語
ハンドルURL	https://hdl.handle.net/11094/98331
PISSN	01683659
eISSN	18734995
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1016/j.jconrel.2024.08.022
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCTERMS.bibliographicCitation	Journal of Controlled Release. 2024, 374, p. 415-424
DC.title	Transplacental delivery of factor IX Fc-fusion protein ameliorates bleeding phenotype of newborn hemophilia B mice
DC.creator	Sakurai, Fuminori
	Iizuka, Shunsuke
	Tsukamoto, Tomohito
	Shiota, Aoi
	Shimizu, Kahori
	Ohashi, Kazuo
	Mizuguchi, Hiroyuki
DC.publisher	Elsevier B.V.
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-10-01
DC.identifier	https://doi.org/10.1016/j.jconrel.2024.08.022
DC.subject	Adenovirus vector
	Factor IX
	Hemophilia
	Transplacental delivery
DC.description	Sakurai F., Iizuka S., Tsukamoto T., et al. Transplacental delivery of factor IX Fc-fusion protein ameliorates bleeding phenotype of newborn hemophilia B mice. Journal of Controlled Release 374, 415 (2024); https://doi.org/10.1016/j.jconrel.2024.08.022.
DCTERMS.abstract	Hemophilia B is an inherited hemorrhagic disorder characterized by a deficiency of blood coagulation factor IX (FIX) that results in abnormal blood coagulation. The blood coagulation is already evident in hemophiliacs at the fetal stage, and thus intracranial hemorrhage and other bleeding complications can occur at birth, leading to sequelae. Therefore, it is important to develop effective treatments for hemophiliacs in utero. In this study, in order to transplacentally deliver FIX from pregnant mice to their fetuses, an improved adenovirus (Ad) vector expressing human FIX fused with the IgG Fc domain (FIX Fc fusion protein), which plays a crucial role in neonatal Fc receptor (FcRn)-mediated transcytosis across the placenta, was intravenously administered to E13.5 pregnant mice. Significant levels of FIX Fc fusion protein were detected in 0-day-old newborn mice whose mothers were administered an Ad vector expressing FIX Fc fusion protein. Wild-type FIX overexpressed in the pregnant mice was not delivered to the fetuses. Plasma FIX levels in the newborn mice were relatively well correlated with those in their mothers, although transplacental delivery efficiencies of FIX Fc fusion protein were slightly reduced when the FIX Fc fusion protein was highly expressed in the mother mice. Plasma FIX levels in the newborn mice were about 3.6–6.4% of those in their mothers, Transplacental delivery of FIX Fc fusion protein to their fetuses successfully improved the blood clotting ability in the newborn mice.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	98331
citation_title	Transplacental delivery of factor IX Fc-fusion protein ameliorates bleeding phenotype of newborn hemophilia B mice
citation_author	Sakurai, Fuminori
	Iizuka, Shunsuke
	Tsukamoto, Tomohito
	Shiota, Aoi
	Shimizu, Kahori
	Ohashi, Kazuo
	Mizuguchi, Hiroyuki
citation_publisher	Elsevier B.V.
citation_language	英語
citation_date	2024-10-01
citation_journal_title	Journal of Controlled Release
citation_volume	374
citation_firstpage	415
citation_lastpage	424
citation_doi	https://doi.org/10.1016/j.jconrel.2024.08.022
citation_public_url	https://hdl.handle.net/11094/98331

Transplacental delivery of factor IX Fc-fusion protein ameliorates bleeding phenotype of newborn hemophilia B mice

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