Development of gene therapy for congenital adrenal hyperplasia using AAV vectors and iPS cells
| Project/Area Number |
16K10005
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | National Center for Child Health and Development |
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Principal Investigator |
Naiki Yasuhiro 国立研究開発法人国立成育医療研究センター, 内科系専門診療部, 医師 (20470007)
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| Co-Investigator(Kenkyū-buntansha) |
勝又 規行 国立研究開発法人国立成育医療研究センター, 分子内分泌研究部, 室長 (10260340)
深見 真紀 国立研究開発法人国立成育医療研究センター, 分子内分泌研究部, 部長 (40265872)
高田 修治 国立研究開発法人国立成育医療研究センター, システム発生・再生医学研究部, 部長 (20382856)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 先天性副腎皮質過形成症 / 遺伝子治療 / アデノウィルス随伴ウィルスベクター / 21水酸化酵素欠損症 / 11β水酸化酵素欠損症 / 先天性副腎皮質過形成 / ips細胞 |
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| Outline of Final Research Achievements |
We have constructed serum type 2 adeno-associated virus vector (AAV2) including CYP21A2. Fibroblasts from 21 hydroxylase deficient patients were infected with the vector and were cultured in the medium with 17 hydroxy progesterone. 17 hydroxy progesterone was converted to 11 deoxycortisol by 21 hydroxylase. Detedted 11 deoxycortisol in medium demonstrated 21 hydroxylase activity had acquired in patients' fibroblasts.
We have also constructed serum type 9 adeno-associated virus vector (AAV9) including Cyp11b1 gene and developed Cyp11b1 deficient mice by gene editing as a model of 11-beta hydroxylase deficiency, respectively. The AAV9 vector was injected directly into the adrenal glands of the model mice and meatured serum deoxycorticosterone and corticosterone. It was demonstrated that serum deoxycorticosterone/corticosterone ratio was improved and lasted for several months. These results suggeted the possibility of gene therapy for congenital adrenal hyperplasia using AAV vectors.
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| Academic Significance and Societal Importance of the Research Achievements |
先天性副腎皮質過形成症は1万出生に1人生まれる比較的頻度の高い先天性疾患で新生児マススクリーニングの対象疾患である。新生児期に診断され生涯にわたるステロイド内服が必要で、重症の塩類喪失型の場合は怠薬などにより副腎不全を来し死に至る。重症型の塩類喪失型と軽症の単純男性型にはわずかな酵素活性の違いしかないため、遺伝子導入によって酵素活性がわずかにでも獲得できれば疾患の軽症化を期待できる。今回研究対象としたAAVベクターはすでに他の単一遺伝子疾患の遺伝子治療やがんへの遺伝子治療の臨床治験が開始されており安全性は確認されていることよりAAVベクターを用いての遺伝子治療は十分に有効性が期待される。
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Report
(4 results)
Research Products
(5 results)
