• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of gene therapy for congenital adrenal hyperplasia using AAV vectors and iPS cells

Research Project

Project/Area Number 16K10005
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionNational Center for Child Health and Development

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)

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)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
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)
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
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.

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。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (5 results)

All 2018 2017 2016

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Extra-adrenal induction of <i>Cyp21a1</i> ameliorates systemic steroid metabolism in a mouse model of congenital adrenal hyperplasia2016

    • Author(s)
      Naiki Y, Miyado M, Horikawa R, Katsumata N, Onodera M, Pang S, Ogata T and Fukami M.
    • Journal Title

      Endocrine Journal

      Volume: 63 Issue: 10 Pages: 897-904

    • DOI

      10.1507/endocrj.EJ16-0112

    • NAID

      130005267899

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] AAVベクターを用いた遺伝子導入による先天性副腎皮質過形成の遺伝子治療の試み2018

    • Author(s)
      内木康博
    • Organizer
      第91回日本内分泌学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] AAVベクターを用いた遺伝子導入による先天性副腎皮質過形成の遺伝子治療の試み2018

    • Author(s)
      内木康博
    • Organizer
      第52回日本小児内分泌学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Induction of CYP21A2 with AAV vector for Gene Therapy of CAH2017

    • Author(s)
      Yasuhiro Naiki
    • Organizer
      The Endocrine Scoiety's 100th Annual Meeting & EXPO
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Introduction of Cyp21a1 with AAV vector ameliorates systemic steroid metabolism in a mouse model of CAH2016

    • Author(s)
      Yasuhiro Naiki
    • Organizer
      第9回アジア太平洋小児内分泌学会
    • Place of Presentation
      東京フォーラム
    • Year and Date
      2016-11-16
    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi