{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:38:05Z","timestamp":1791639485008,"version":"4.3.4"},"reference-count":66,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"842","funder":[{"DOI":"10.13039\/100018156","name":"Sangamo Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,3,25]]},"abstract":"<jats:p>\n                    Peripheral neuropathies are estimated to affect several million patients in the US, with no long-lasting therapy currently available. In humans, the Nav1.7 sodium channel, encoded by the\n                    <jats:italic toggle=\"yes\">SCN9A<\/jats:italic>\n                    gene, is involved in a spectrum of inherited neuropathies and has emerged as a promising target for analgesic drug development. The development of a selective Nav1.7 inhibitor has been challenging, in part because of structural similarities with other Nav channels. Here, we present preclinical studies for a genomic medicine approach using engineered zinc finger repressors (ZFRs) specifically targeting the human\/nonhuman primate (NHP)\n                    <jats:italic toggle=\"yes\">SCN9A<\/jats:italic>\n                    gene. Adeno-associated virus (AAV)\u2013mediated delivery of ZFRs in human induced pluripotent stem cell (iPSC)\u2013derived neurons resulted in the reduction of\n                    <jats:italic toggle=\"yes\">SCN9A<\/jats:italic>\n                    with no detectable off-target activity. In the spared nerve injury (SNI) neuropathic pain mouse model, AAV-ZFR administration resulted in \u226470% repression of\n                    <jats:italic toggle=\"yes\">Scn9a<\/jats:italic>\n                    in mouse dorsal root ganglia (DRGs) and was associated with reduction in pain hypersensitivity. AAV9-mediated intrathecal-lumbar (IT-lumbar) delivery of ZFRs in NHPs demonstrated repression of\n                    <jats:italic toggle=\"yes\">SCN9A<\/jats:italic>\n                    in bulk DRG tissue and single-cell levels in nociceptors 1 month after treatment. A lead AAV9-ZFR investigational product, ST-503, was developed and further evaluated in a 6-month study in NHPs. ST-503 administration by IT-lumbar infusion resulted in 50% repression of\n                    <jats:italic toggle=\"yes\">SCN9A<\/jats:italic>\n                    in bulk DRG tissue at 6 months without findings of dose-limiting toxicity or impact on neurological and cardiac safety pharmacology. Together, our results support further development of an AAV-delivered ZFR as a potential therapy for patients with peripheral neuropathies.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adu0217","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T17:58:21Z","timestamp":1774461501000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Engineered zinc finger repressors induce a prolonged and selective repression of\n                    <i>SCN9A<\/i>\n                    in nociceptors of nonhuman primates"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9697-3792","authenticated-orcid":true,"given":"Mohammad","family":"Samie","sequence":"first","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toufan","family":"Parman","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihika","family":"Jalan","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2120-4160","authenticated-orcid":true,"given":"Jisoo","family":"Lee","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Dunn","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9371-499X","authenticated-orcid":true,"given":"Jason","family":"Eshleman","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8672-7289","authenticated-orcid":true,"given":"Dianna Baldwin","family":"Vidales","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Kennard","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josh","family":"Holter","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1654-7161","authenticated-orcid":true,"given":"Brian","family":"Jones","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4673-1312","authenticated-orcid":true,"given":"Yonghua","family":"Pan","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2921-5311","authenticated-orcid":true,"given":"Marina","family":"Falaleeva","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6245-0013","authenticated-orcid":true,"given":"Sarah","family":"Hinkley","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5040-9505","authenticated-orcid":true,"given":"Alicia","family":"Goodwin","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy","family":"Chen","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumita","family":"Bhardwaj","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Ward","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0861-7326","authenticated-orcid":true,"given":"Michael","family":"Trias","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Chikere","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhura","family":"Som","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmei","family":"Lu","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1333-1671","authenticated-orcid":true,"given":"Sandeep","family":"Yadav","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5106-0519","authenticated-orcid":true,"given":"Jason","family":"Fontenot","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4439-0085","authenticated-orcid":true,"given":"Bryan","family":"Zeitler","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0678-8153","authenticated-orcid":true,"given":"Amy","family":"Pooler","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3601-9235","authenticated-orcid":true,"given":"Kathleen","family":"Meyer","sequence":"additional","affiliation":[{"name":"Sangamo Therapeutics Inc., Richmond, CA 94804, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2011.09.014"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2005.11.008"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2011.06.017"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.2165\/00019053-200927020-00002"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0972"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S207610"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm501981g"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2003-4-3-207"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33297"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2695-04.2004"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.012153"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.10.006"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05413"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2007.08.004"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3404"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.01.047"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm160"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001227"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-019-00832-2"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature21683"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay9056"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0478-3"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe1611"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2022.100119"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.10.4509"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-10-74"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad7653"},{"key":"e_1_3_2_29_2","first-page":"3092","article-title":"The spared nerve injury (SNI) model of induced mechanical allodynia in mice","author":"Richner M.","year":"2011","unstructured":"M. Richner, O. J. Bjerrum, A. Nykjaer, C. B. Vaegter, The spared nerve injury (SNI) model of induced mechanical allodynia in mice. J. Vis. Exp., 3092 (2011).","journal-title":"J. Vis. Exp."},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001973"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2018.015"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2018.06.004"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2018.06.003"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2020.269"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2022.01.013"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aba9188"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2010.02.034"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.2"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2018.08.005"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70251-0"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/jgf2.5"},{"key":"e_1_3_2_42_2","first-page":"CD006146","article-title":"Opioids for neuropathic pain","volume":"2013","author":"McNicol E. D.","year":"2013","unstructured":"E. D. McNicol, A. Midbari, E. Eisenberg, Opioids for neuropathic pain. Cochrane Database Syst. Rev. 2013, CD006146 (2013).","journal-title":"Cochrane Database Syst. Rev."},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.08.011"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.101971"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S388896"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15327"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/d41573-019-00065-0"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b01906"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-021-00444-w"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.516"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvy210"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.274035"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2020.167"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22485"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1795"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.067331"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2020.04.001"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1001007"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.831062"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12871-016-0215-0"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1995-7645(14)60352-7"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.148"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa020"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.106"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.3390\/ani12172304"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2217800120"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-6-83"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adu0217","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T17:58:28Z","timestamp":1774461508000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adu0217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":66,"journal-issue":{"issue":"842","published-print":{"date-parts":[[2026,3,25]]}},"alternative-id":["10.1126\/scitranslmed.adu0217"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adu0217","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]},"assertion":[{"value":"2024-10-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-21","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadu0217"}}