{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:42:59Z","timestamp":1779345779201,"version":"3.51.4"},"reference-count":24,"publisher":"SAGE Publications","issue":"15-16","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:p>\n                    Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by steroidogenic enzymes containing monogenetic defects. Most steroidogenic enzymes are cytochrome P450 groups that can be categorized as microsomal P450s, including 21-hydroxylase and 17\u03b1-hydroxylase\/17,20 lyase, and mitochondrial P450s, including 11\u03b2-hydroxylase. It has been shown that ectopic administration of\n                    <jats:italic toggle=\"yes\">Cyp21a1<\/jats:italic>\n                    ameliorates steroid metabolism in 21-hydroxylase-deficient mice. However, the effectiveness of this approach for mitochondrial P450 has not yet been evaluated. In this study, primary fibroblasts from patients with 21-hydroxylase deficiency (CYP21A2D) (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u20094), 17\u03b1-hydroxylase\/17,20 lyase deficiency (CYP17A1D) (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u20091), and 11\u03b2-hydroxylase deficiency (CYP11B1D) (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u20091) were infected with adeno-associated virus type 2 (AAV2) vectors. Steroidogenic enzymatic activity was not detected in the AAV2-infected CYP11B1D fibroblasts. Induced pluripotent stem cells (iPSCs) of CYP11B1D were established and differentiated into adrenocortical cells by induction of the\n                    <jats:italic toggle=\"yes\">NR5A1<\/jats:italic>\n                    gene. Adrenocortical cells established from iPSCs of CYP11B1D (CYP11B1D-iPSCs) were infected with an AAV type 9 (AAV9) vector containing\n                    <jats:italic toggle=\"yes\">CYP11B1<\/jats:italic>\n                    and exhibited 11\u03b2-hydroxylase activity. For an\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    evaluation, we knocked out\n                    <jats:italic toggle=\"yes\">Cyp11b1<\/jats:italic>\n                    in mice by using the CRISPR\/Cas9 method. Direct injection of\n                    <jats:italic toggle=\"yes\">Cyp11b1<\/jats:italic>\n                    -containing AAV9 vectors into the adrenal gland of\n                    <jats:italic toggle=\"yes\">Cyp11b1<\/jats:italic>\n                    -deficient mice significantly reduced serum 11-deoxycorticosterone\/corticosterone ratios at 4 weeks after injection and the effect was prolonged for up to 12 months. This study indicated that CYP11B1D could be ameliorated by gene induction in the adrenal glands, which suggests that a defective-enzyme-dependent therapeutic strategy for CAH would be required. Defects in microsomal P450, including CYP21A2D and CYP17A1D, can be treated with extra-adrenal gene induction. However, defects in mitochondrial P450, as represented by CYP11B1D, may require adrenal gene induction.\n                  <\/jats:p>","DOI":"10.1089\/hum.2022.005","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T06:49:07Z","timestamp":1657867747000},"page":"801-809","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["Adeno-Associated Virus-Mediated Gene Therapy for Patients' Fibroblasts, Induced Pluripotent Stem Cells, and a Mouse Model of Congenital Adrenal Hyperplasia"],"prefix":"10.1177","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6338-895X","authenticated-orcid":false,"given":"Yasuhiro","family":"Naiki","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism, National Center for Child Health and Development, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mami","family":"Miyado","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miyuki","family":"Shindo","sequence":"additional","affiliation":[{"name":"Division of Laboratory Animal Resources, National Research Institute for Child Health and Development, Tokyo, Japan; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reiko","family":"Horikawa","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, National Center for Child Health and Development, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichi","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Division of Urology, National Center for Child Health and Development, Tokyo, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriyuki","family":"Katsumata","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuji","family":"Takada","sequence":"additional","affiliation":[{"name":"Department of Systems BioMedicine, National Research Institute for Child Health and Development, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidenori","family":"Akutsu","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, National Research Institute for Child Health and Development, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafumi","family":"Onodera","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, National Research Institute for Child Health and Development, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maki","family":"Fukami","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-18-0279"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra021561"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-01865"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.9.2819"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1201\/en135.4.1470"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3301018"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ16-0112"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.77.6.7903314"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep03594"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1293"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2010.11.025"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1225829"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232033"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep05396"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.140.7.6755"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2009.06.007"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.3.699"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2019.01.008"},{"key":"e_1_3_5_20_2","unstructured":"Melmed S Auchus R Goldfine AB et al. eds. Principles of Endocrinology. Williams Textbook of Endocrinology 14th ed. Philadelphia: Elsevier Saunders Co. Ltd; 2020; pp. 2\u201312."},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2017.203"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2009.148"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.01.003"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvab048.165"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.1543"}],"container-title":["Human Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/hum.2022.005","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2022.005","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2022.005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:56:13Z","timestamp":1777449373000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/hum.2022.005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8]]},"references-count":24,"journal-issue":{"issue":"15-16","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1089\/hum.2022.005"],"URL":"https:\/\/doi.org\/10.1089\/hum.2022.005","relation":{},"ISSN":["1043-0342","1557-7422"],"issn-type":[{"value":"1043-0342","type":"print"},{"value":"1557-7422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8]]}}}