Extra-adrenal expression of Cyp21a1 for gene therapy of congenital adrenal hyperplasia

• Project/Area Number: 22591148
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: NAIKI Yasuhiro 独立行政法人国立成育医療研究センター, 内分泌代謝科, 医師 (20470007)
• Co-Investigator(Kenkyū-buntansha): 勝又 規行 独立行政法人国立成育医療研究センター研究所, 基礎内分泌研究室 (10260340) ; 深見 真紀 独立行政法人国立成育医療研究センター研究所, 分子内分泌研究部 (40265872) ; 小野寺 雅史 国立成育医療研究センター研究所, 成育遺伝研究部 (10334062)
• Project Period (FY): 2010-04-01 – 2013-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 遺伝子治療 / 副腎皮質過形成 / レトロウィルスベクター / アデノウィルス関連ウィルスベクター / 先天性副腎皮質過形成 / ips細胞 / 21水酸化酵素欠損症 / 線維芽細胞 / 小児内分泌 / ウィルスベクター

Research Abstract

21-hydorxylase deficient (Cyp21a1D) mice were made by breeding with heterozygous of H-2aw18 haplotype mice. Retrovirus vector containing mouse Cyp21a1 cDNA was constructed and transmitted to fibroblasts cultured from 21OHD mice. Cyp21a1-induced fibroblasts were injected into Cyp21a1D mice. Adenoassociated virus vector containing Cyp21a cDNA (AAV-Cyp21a1) was constructed with pAAV-CMV-shuttle and injected into limbs muscles of 21OHD mice. Serum P4 and DOC concentrations were also measured before and after injection. Transplantation of the transgenic fibroblasts into Cyp21a1D mice showed slight change serum P4/DOC ratio. Transgenic 21OHD mice with AAV-Cyp21a1 showed increase DOC production and decreased P4/DOC ratio (1223 to 39.2) at 4weeks after injection. We succeeded recovering 21OH activity steroid production in in Cyp21a1D mice by introducing Cyp21a1 gene into muscle with adenoassociated virus vectors for 4 weeks.

Research Products

• [Journal Article] Novel intronic CYP21A2 mutation in Japanese patient with classic salt-wasting steroid 21-hydroxylase deficiency (2010)
  • Author(s): Noriyuki Katsumata
  • Journal Title: Metabolism Volume: 59 Pages: 1628-1632