{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:02:43Z","timestamp":1780444963086,"version":"3.54.1"},"reference-count":58,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SERB CRG","award":["CRG\/2021\/000147"],"award-info":[{"award-number":["CRG\/2021\/000147"]}]},{"name":"SERB CRG","award":["5\/4\/8-28\/CD\/DSG\/2022-NCD-II"],"award-info":[{"award-number":["5\/4\/8-28\/CD\/DSG\/2022-NCD-II"]}]},{"name":"SERB CRG","award":["BT\/RLF\/Rentry\/38\/2019"],"award-info":[{"award-number":["BT\/RLF\/Rentry\/38\/2019"]}]},{"name":"ICMR","award":["CRG\/2021\/000147"],"award-info":[{"award-number":["CRG\/2021\/000147"]}]},{"name":"ICMR","award":["5\/4\/8-28\/CD\/DSG\/2022-NCD-II"],"award-info":[{"award-number":["5\/4\/8-28\/CD\/DSG\/2022-NCD-II"]}]},{"name":"ICMR","award":["BT\/RLF\/Rentry\/38\/2019"],"award-info":[{"award-number":["BT\/RLF\/Rentry\/38\/2019"]}]},{"name":"DBT Ramalingaswami fellowship","award":["CRG\/2021\/000147"],"award-info":[{"award-number":["CRG\/2021\/000147"]}]},{"name":"DBT Ramalingaswami fellowship","award":["5\/4\/8-28\/CD\/DSG\/2022-NCD-II"],"award-info":[{"award-number":["5\/4\/8-28\/CD\/DSG\/2022-NCD-II"]}]},{"name":"DBT Ramalingaswami fellowship","award":["BT\/RLF\/Rentry\/38\/2019"],"award-info":[{"award-number":["BT\/RLF\/Rentry\/38\/2019"]}]},{"name":"BRIC-NII","award":["CRG\/2021\/000147"],"award-info":[{"award-number":["CRG\/2021\/000147"]}]},{"name":"BRIC-NII","award":["5\/4\/8-28\/CD\/DSG\/2022-NCD-II"],"award-info":[{"award-number":["5\/4\/8-28\/CD\/DSG\/2022-NCD-II"]}]},{"name":"BRIC-NII","award":["BT\/RLF\/Rentry\/38\/2019"],"award-info":[{"award-number":["BT\/RLF\/Rentry\/38\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hepatic lipogenesis combined with elevated endoplasmic reticulum (ER) stress is central to non-alcoholic steatohepatitis (NASH). However, the therapeutic targeting of key molecules is considerably less accomplished. Adeno-associated virus (AAV)-mediated gene therapies offer a new solution for various human ailments. Comprehensive bio-functional validation studies are essential to assess the impact of AAVs in the target organ for developing both preclinical and clinical gene therapy programs. Here, we have established a robust and efficient protocol for high-titer AAV production to enable detailed Selective ORgan Targeting (SORT) of AAV1, 5, 7, and 8 in vivo. Our results for in vivo SORT showed single organ (liver) targeting by AAV8, no organ targeting by AAV1, and dual organ transduction (liver-brain and liver-VAT) by AAV5 and AAV7. Using a human dataset and preclinical murine models of NASH, we identified an inverse correlation between ER stress-triggered CRELD2 and the de novo lipogenesis driver FASN. Furthermore, liver-specific silencing of CRELD2 via AAV8-shCreld2 strongly supports the contribution of CRELD2 to de novo lipogenesis through FASN regulation. Thus, our study demonstrates a robust method for producing clinically translatable AAVs that could be readily adapted for liver and\/or liver-VAT or liver-brain targeted gene therapy.<\/jats:p>","DOI":"10.3390\/cells14050372","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T03:26:21Z","timestamp":1741058781000},"page":"372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development and Validation of AAV-Mediated Liver, Liver-VAT, and Liver-Brain SORT and Therapeutic Regulation of FASN in Hepatic De Novo Lipogenesis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0081-1093","authenticated-orcid":false,"given":"Ratulananda","family":"Bhadury","sequence":"first","affiliation":[{"name":"Immuno-Inflammation Laboratory, National Institute of Immunology (BRIC-NII), Aruna Asaf Ali Marg, New Delhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9229-2375","authenticated-orcid":false,"given":"Mohammad","family":"Athar","sequence":"additional","affiliation":[{"name":"Immuno-Inflammation Laboratory, National Institute of Immunology (BRIC-NII), Aruna Asaf Ali Marg, New Delhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4184-3896","authenticated-orcid":false,"given":"Pooja","family":"Mishra","sequence":"additional","affiliation":[{"name":"Immuno-Inflammation Laboratory, National Institute of Immunology (BRIC-NII), Aruna Asaf Ali Marg, New Delhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6737-6254","authenticated-orcid":false,"given":"Chayanika","family":"Gogoi","sequence":"additional","affiliation":[{"name":"Immuno-Inflammation Laboratory, National Institute of Immunology (BRIC-NII), Aruna Asaf Ali Marg, New Delhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubham","family":"Sharma","sequence":"additional","affiliation":[{"name":"Immuno-Inflammation Laboratory, National Institute of Immunology (BRIC-NII), Aruna Asaf Ali Marg, New Delhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6600-6390","authenticated-orcid":false,"given":"Devram S.","family":"Ghorpade","sequence":"additional","affiliation":[{"name":"Immuno-Inflammation Laboratory, National Institute of Immunology (BRIC-NII), Aruna Asaf Ali Marg, New Delhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.cell.2018.08.020","article-title":"ER Stress Drives Lipogenesis and Steatohepatitis via Caspase-2 Activation of S1P","volume":"175","author":"Kim","year":"2018","journal-title":"Cell"},{"key":"ref_2","unstructured":"(2025, January 20). 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