{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:37:53Z","timestamp":1790336273230,"version":"4.1.0"},"posted":{"date-parts":[[2026,3,9]]},"group-title":"Neuroscience","reference-count":75,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/01d35cw23","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/0515k5w36","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Edwards PhD Studentship in Pain Research"},{"award":["U19NS130617"],"award-info":[{"award-number":["U19NS130617"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01NS119476"],"award-info":[{"award-number":["R01NS119476"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DP1DA054343"],"award-info":[{"award-number":["DP1DA054343"]}],"id":[{"id":"https:\/\/ror.org\/00fq5cm18","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U01EY034709"],"award-info":[{"award-number":["U01EY034709"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Massachusetts General Brigham Gene and Cell Therapy Institute"},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Chronic pain conditions are often driven by hyperexcitability of nociceptors, the peripheral sensory neurons that detect noxious stimuli. Recent single-cell transcriptomic studies have begun to clarify the molecular identity of distinct peripheral sensory neuron subtypes, but tools that restrict transgene expression to nociceptors while sparing other dorsal root ganglion (DRG) subtypes remain limited. Here, we combined single-nucleus multi-omic profiling of human and mouse DRG with\n                  <jats:italic>in vivo<\/jats:italic>\n                  AAV enhancer screening to identify\n                  <jats:italic>cis<\/jats:italic>\n                  -regulatory elements that drive biased AAV expression in mouse DRG nociceptors and human iPSC-derived nociceptors. We then validated that an enhancer AAV designed to express K\n                  <jats:sub>ir<\/jats:sub>\n                  2.1 preferentially in nociceptors reduces DRG neuronal excitability. Leveraging these multi-omic datasets, we trained a sequence-based model to decode the\n                  <jats:italic>cis<\/jats:italic>\n                  -regulatory logic of nociceptors, enabling both the prioritization of native candidate elements and the design of synthetic enhancers with a range of nociceptor targeting properties. Together, these cross-species multi-omic resources define conserved DRG regulatory programs and provide a viral toolkit for pain research with potential translational applications for patients with refractory pain.\n                <\/jats:p>","DOI":"10.64898\/2026.03.05.709931","type":"posted-content","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T20:00:16Z","timestamp":1773086416000},"source":"Crossref","is-referenced-by-count":1,"title":["Multi-omic profiling of human and mouse dorsal root ganglia enables targeted gene delivery to nociceptors"],"prefix":"10.64898","author":[{"given":"Lily S.","family":"He","sequence":"first","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parth","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamsuddin A.","family":"Bhuiyan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelia","family":"Semizoglou","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joohyun","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay X. J.","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chayse","family":"Arnhold","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Difei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin","family":"Griesemer","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo Jeong","family":"Yong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna","family":"Jayne","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangeline","family":"Gilmer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Pantaleo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lite","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika K.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selwyn","family":"Jayakar","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Wainger","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinisa","family":"Hrvatin","sequence":"additional","affiliation":[{"name":"Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA"},{"name":"Howard Hughes Medical Institute, Massachusetts Institute of Technology, 14 Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0206-2101","authenticated-orcid":false,"given":"William","family":"Renthal","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"NIH PRECISION Human Pain Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026031412300596000_2026.03.05.709931v2.1","first-page":"100557","article-title":"The Lancet Regional Health \u2013 Americas. 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