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However, lifelong ART poses challenges. These include social stigma, medication costs, drug accessibility, mental health, and drug\u2010related toxicities. Moreover, ART does not eliminate latent HIV\u20101 DNA. Viral persistence in tissue and cell reservoirs results in viral rebound after ART interruption. New strategies are required to achieve a functional HIV\u20101 cure. To excise latent HIV\u20101, C\u2010X\u2010C motif chemokine receptor 4 (CXCR4) ligand\u2010decorated lymphoid tissue\u2010targeting lipid nanoparticles (LNPs) for CRISPR\u2010Cas9\/gRNA delivery are developed. These LNPs enhance mRNA translation and demonstrate CXCR4\u2010mediated improved uptake to eliminate HIV\u20101 DNA in infected CD4+ T cells. LNPs also facilitate targeted drug delivery, achieving HIV\u20101 DNA excision in ART\u2010treated, infected humanized mice. This study emphasizes the potential of tissue and cell\u2010targeted LNPs for effective HIV\u20101 DNA excision.<\/jats:p>","DOI":"10.1002\/adhm.202501190","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T07:11:52Z","timestamp":1752477112000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Lymphoid and CXCR4 Cell Targeted Lipid Nanoparticles Facilitate HIV\u20101 Proviral DNA Excision"],"prefix":"10.1002","volume":"14","author":[{"given":"Sudipta","family":"Panja","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha NE 68198 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubaba A.","family":"Zaman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha NE 68198 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha NE 68198 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milankumar","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha NE 68198 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santhi","family":"Gorantla","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha NE 68198 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasanta K.","family":"Dash","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha NE 68198 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7831-0370","authenticated-orcid":false,"given":"Howard E.","family":"Gendelman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha NE 68198 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"e_1_2_9_1_1","unstructured":"WHO HIV Factsheets https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/hiv\u2010aids accessed."},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-0181-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1295-1284"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/387183a0"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199904160-00008"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000038768"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41434\u2010023\u201000413\u20101"},{"key":"e_1_2_9_8_1","first-page":"1","volume":"3","author":"Gorman J.","year":"2020","journal-title":"Cell Rep."},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13072-019-0267-8"},{"key":"e_1_2_9_10_1","unstructured":"NIH CAR\u2010T Cells for HIV Infection https:\/\/clinicaltrials.gov\/study\/NCT04648046 (accessed: Jan2024)."},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14670-w"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-024-01010-8"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2021.1865302"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10366-y"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2217887120"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.03.012"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep22555"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41434-023-00410-4"},{"key":"e_1_2_9_19_1","unstructured":"NIH Study of EBT\u2010101 in Aviremic HIV\u20101 Infected Adults on Stable ARThttps:\/\/clinicaltrials.gov\/study\/NCT05144386 (accessed: December2024)."},{"key":"e_1_2_9_20_1","unstructured":"E. 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