分子病態治療研究センター

大庭 賢二

オオバ ケンジ  (Kenji Ohba)

基本情報

所属
自治医科大学 分子病態治療研究センター 遺伝子治療研究部 講師
学位
博士(医学)(2008年3月 東京医科歯科大学)

研究者番号
20759576
ORCID ID
 https://orcid.org/0000-0002-4936-8186
J-GLOBAL ID
201501081538096585
researchmap会員ID
B000246215

外部リンク

論文

 35
  • Yoshihide Sehara, Yuki Hashimotodani, Ryota Watano, Kenji Ohba, Ryosuke Uchibori, Kuniko Shimazaki, Kensuke Kawai, Hiroaki Mizukami
    Molecular Neurobiology 2024年4月27日  
  • Yuka Hayashi, Yoshihide Sehara, Ryota Watano, Kenji Ohba, Yuki Takayanagi, Yoshio Sakiyama, Kazuhiro Muramatsu, Hiroaki Mizukami
    Human Gene Therapy 35(5-6) 192-201 2024年3月1日  
  • Kenji Ohba, Hiroaki Mizukami
    STAR Protocols 4(4) 102542-102542 2023年12月15日  査読有り招待有り筆頭著者責任著者
  • Yuka Hayashi, Yoshihide Sehara, Ryota Watano, Kenji Ohba, Yuki Takayanagi, Kazuhiro Muramatsu, Yoshio Sakiyama, Hiroaki Mizukami
    The Journal of Gene Medicine e3560 2023年6月30日  査読有り
    BACKGROUND: Fabry disease (FD) is an inherited lysosomal storage disease caused by deficiency of α-galactosidase A (α-Gal A) encoded by the GLA gene. The symptoms of FD occur as a result of the accumulation of globotriaosylceramide (Gb3), comprising a substrate of α-Gal A, in the organs. Adeno-associated virus (AAV)-mediated gene therapy is a promising treatment for FD. METHODS: α-Gal A knockout (GLAko) mice were injected intravenously with AAV2 (1 × 1011 viral genomes [vg]) or AAV9 (1 × 1011 or 2 × 1012 vg) vectors carrying human GLA (AAV-hGLA), and plasma, brain, heart, liver and kidney were tested for α-Gal A activity. The vector genome copy numbers (VGCNs) and Gb3 content in each organ were also examined. RESULTS: The plasma α-Gal A enzymatic activity was three-fold higher in the AAV9 2 × 1012 vg group than wild-type (WT) controls, which was maintained for up to 8 weeks after injection. In the AAV9 2 × 1012 vg group, the level of α-Gal A expression was high in the heart and liver, intermediate in the kidney, and low in the brain. VGCNs in the all organs of the AAV9 2 × 1012 vg group significantly increased compared to the phosphate-buffered-saline (PBS) group. Although Gb3 in the heart, liver and kidney of the AAV9 2 × 1012 vg was reduced compared to PBS group and AAV2 group, and the amount of Gb3 in the brain was not reduced. CONCLUSIONS: Systemic injection of AAV9-hGLA resulted in α-Gal A expression and Gb3 reduction in the organs of GLAko mice. To expect a higher expression of α-Gal A in the brain, the injection dosage, administration route and the timing of injection should be reconsidered.
  • Kenji Ohba, Yoshihide Sehara, Tatsuji Enoki, Junichi Mineno, Keiya Ozawa, Hiroaki Mizukami
    iScience 26(4) 106487-106487 2023年3月  査読有り筆頭著者責任著者

MISC

 29

書籍等出版物

 2

講演・口頭発表等

 45

所属学協会

 6

共同研究・競争的資金等の研究課題

 7

産業財産権

 2

メディア報道

 2

その他

 1