{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T06:58:40Z","timestamp":1772089120425,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T00:00:00Z","timestamp":1757721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT)","award":["NRF-2020R1C1C1013849"],"award-info":[{"award-number":["NRF-2020R1C1C1013849"]}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT)","award":["6-2018-0173"],"award-info":[{"award-number":["6-2018-0173"]}]},{"name":"CMB-Yuhan research grant of Yonsei University College of Medicine","award":["NRF-2020R1C1C1013849"],"award-info":[{"award-number":["NRF-2020R1C1C1013849"]}]},{"name":"CMB-Yuhan research grant of Yonsei University College of Medicine","award":["6-2018-0173"],"award-info":[{"award-number":["6-2018-0173"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Endometriosis is a chronic estrogen-dependent condition with limited treatment options, often requiring surgery and long-term hormonal therapy that may impair ovarian function. Despite advancements in gene therapy for other diseases, its application in endometriosis remains largely unexplored. This study aimed to evaluate the potential of adeno-associated virus (AAV) vectors for targeted gene therapy in endometriosis. We screened multiple AAV serotypes for infectivity in primary human ectopic and eutopic endometrial cells as well as normal ovarian stromal cells. AAV serotype 3 (AAV3) demonstrated selective infectivity toward endometrial cells while sparing ovarian tissue. AAV3-mediated delivery of small interfering RNA targeting estrogen receptor 2 reduced Estrogen receptor beta (ER\u03b2) expression to 27% in ectopic and 49% in eutopic cells. Under estradiol and inflammatory stimulation, ER\u03b2 knockdown led to modest reductions in cellular metabolic activity in eutopic cells, whereas effects in ectopic cells did not reach statistical significance. Dual targeting of ER\u03b2 and prostaglandin-endoperoxide synthase 2 (PTGS2) showed numerically lower metabolic activity than controls under some conditions but without consistent statistical significances. These findings suggest that AAV3 can serve as an ovary-sparing, endometriosis-specific vector that facilitates gene silencing while yielding limited phenotypic effects. This gene delivery system may provide a basis for developing future gene-based therapies for endometriosis.<\/jats:p>","DOI":"10.3390\/microorganisms13092144","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T07:56:51Z","timestamp":1757923011000},"page":"2144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of Adeno-Associate Virus (AAV) Serotype for Endometriosis Therapy and Effect of AAV-Mediated RNAi Delivery on Gene Expression and Cell Proliferation in In Vitro Endometrial Cell Culture"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7958-0436","authenticated-orcid":false,"given":"Jin Kyung","family":"Baek","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaekyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9168-0408","authenticated-orcid":false,"given":"Yun Soo","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3404-0484","authenticated-orcid":false,"given":"Seokkyo","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1056\/NEJMra0804690","article-title":"Mechanisms of disease endometriosis","volume":"360","author":"Bulun","year":"2009","journal-title":"N. 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