{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:13:36Z","timestamp":1792725216583,"version":"4.5.0"},"reference-count":34,"publisher":"American Chemical Society (ACS)","issue":"11","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100006464","name":"Birla Institute of Technology and Science, Pilani","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100006464","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Psoriasis is a chronic, incurable inflammatory skin disease characterized by immune cell infiltration, aberrant keratinocyte differentiation, and enhanced angiogenesis. Overexpression of the vascular endothelial growth factor-A (VEGF-A) gene promotes angiogenesis and is essential for endothelial cell migration, adhesion, and proliferation. Therefore, downregulating VEGF-A represents a promising therapeutic strategy for angiogenesis-related disorders. We investigated the application of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)\/CRISPR-associated protein 9 (Cas9) ribonucleoprotein complexes (sgRNA\/eGFP-Cas9 RNPs) targeting VEGF-A in psoriasis. To enable efficient delivery in vitro and in vivo, we developed lipopolymeric nanoplexes (NPXs) encapsulating sgRNA\/eGFP-Cas9 RNPs. These NPXs exhibited a particle size of 142.2 nm (polydispersity index: 0.144), a zeta potential of +4.27 mV, and achieved &amp;gt;70% transfection efficiency in HaCaT (human immortalized keratinocyte) cells. Ex vivo skin permeation studies demonstrated 66% of permeation after 24 h. The optimized NPX formulation was incorporated into a Carbopol-based gel, which displayed non-Newtonian, shear-thinning behavior with variable thixotropy and achieved 48% of skin permeation after 24 h. In vivo efficacy assessment in an imiquimod-induced psoriasis model in Swiss albino mice showed significantly improved Psoriasis Area and Severity Index (PASI) scores, reduced epidermal damage, and suppressed keratinocyte proliferation compared to naked RNPs and blank gel controls. Gene editing analysis revealed an indel frequency of 40.7% by T7 endonuclease I assay and 14% by Sanger sequencing. Enhanced cellular uptake, efficient skin permeation and retention, and improved therapeutic efficacy collectively highlight the potential of NPX-mediated CRISPR\/Cas9 delivery as a noninvasive strategy for psoriasis treatment.<\/jats:p>","DOI":"10.1021\/acsabm.5c01478","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:48:14Z","timestamp":1761922094000},"page":"10137-10157","source":"Crossref","is-referenced-by-count":4,"title":["Lipopolymeric Nanoplex-Mediated CRISPR\/Cas9 Delivery\nfor VEGF-A Knockdown in Psoriatic Angiogenesis"],"prefix":"10.1021","volume":"8","author":[{"given":"Abhay","family":"Tharmatt","sequence":"first","affiliation":[{"name":"Birla Institute of Technology and Science Pilani , , Vidya Vihar, , ,","place":["Pilani, Rajasthan, India, 333031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Guha","sequence":"additional","affiliation":[{"name":"Birla Institute of Technology and Science Pilani , , Vidya Vihar, , ,","place":["Pilani, Rajasthan, India, 333031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3351-7148","authenticated-orcid":true,"given":"Tushar","family":"Kumeria","sequence":"additional","affiliation":[{"name":"University of New South Wales , , , ,","place":["Sydney, New South Wales, Australia, 2052"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushil","family":"Yadav","sequence":"additional","affiliation":[{"name":"Birla Institute of Technology and Science Pilani , , Vidya Vihar, , ,","place":["Pilani, Rajasthan, India, 333031"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3344-9579","authenticated-orcid":true,"given":"Anupama","family":"Mittal","sequence":"additional","affiliation":[{"name":"Birla Institute of Technology and Science Pilani , , Vidya Vihar, , ,","place":["Pilani, Rajasthan, India, 333031"]},{"name":"National Institute of Pharmaceutical Education and Research , , , ,","place":["SAS Nagar, Punjab, India, 160062"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4174-7664","authenticated-orcid":true,"given":"Deepak","family":"Chitkara","sequence":"additional","affiliation":[{"name":"Birla Institute of Technology and Science Pilani , , Vidya Vihar, , ,","place":["Pilani, Rajasthan, India, 333031"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"2026072914075819600_cit1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3238\/arztebl.2009.0011","article-title":"Psoriasis\u2500new insights into pathogenesis and treatment","volume":"106","author":"Mrowietz","year":"2009","journal-title":"Dtsch. Arztebl. Int."},{"key":"2026072914075819600_cit2","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.3390\/ijms20061475","article-title":"Psoriasis pathogenesis\nand treatment","volume":"20","author":"Rendon","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"2026072914075819600_cit3","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/bjd.19380","article-title":"Role of regulatory\nT cells in psoriasis\npathogenesis and treatment","volume":"184","author":"Nussbaum","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"2026072914075819600_cit4","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s12016-017-8634-3","article-title":"Unmet needs\nin the field of psoriasis: pathogenesis\nand treatment","volume":"55","author":"Boehncke","year":"2018","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"2026072914075819600_cit5","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax5849","article-title":"Epidermal\nautonomous\nVEGFA\/Flt1\/Nrp1 functions mediate psoriasis-like disease","volume":"6","author":"Benhadou","year":"2020","journal-title":"Sci. Adv."},{"key":"2026072914075819600_cit6","doi-asserted-by":"publisher","first-page":"104365","DOI":"10.1016\/j.jddst.2023.104365","article-title":"Topical delivery of Anti-VEGF nanomedicines for treating\npsoriasis","volume":"83","author":"Tharmatt","year":"2023","journal-title":"J. Drug Delivery Sci. Technol."},{"key":"2026072914075819600_cit7","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.ajps.2022.02.001","article-title":"Delivery Strategies\nfor CRISPR\/Cas\nGenome Editing Tool for Retinal Dystrophies: Challenges and Opportunities","volume":"17","author":"Lohia","year":"2022","journal-title":"Asian J. Pharm. Sci."},{"key":"2026072914075819600_cit8","doi-asserted-by":"publisher","first-page":"353","DOI":"10.2147\/BTT.S326422","article-title":"Mechanism and Applications of CRISPR\/Cas-9-Mediated\nGenome Editing","volume":"15","author":"Asmamaw","year":"2021","journal-title":"Biologics"},{"key":"2026072914075819600_cit9","doi-asserted-by":"publisher","first-page":"9013","DOI":"10.3390\/ijms24109013","article-title":"CRISPR-Mediated In Situ Introduction or Integration of F9-Padua in\nHuman iPSCs for Gene Therapy of Hemophilia B","volume":"24","author":"Tang","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"2026072914075819600_cit10","doi-asserted-by":"publisher","first-page":"8051","DOI":"10.21203\/RS.3.RS-2540755\/V1","article-title":"Shuttle\nPeptide Delivers\nBase Editor RNPs to Rhesus Monkey Airway Epithelial Cells In Vivo","volume":"14","author":"Kulhankova","year":"2023","journal-title":"Nat. Commun."},{"key":"2026072914075819600_cit11","doi-asserted-by":"publisher","first-page":"281","DOI":"10.12688\/f1000research.23185.2","article-title":"Gene editing in\ndermatology: Harnessing CRISPR for\nthe treatment of cutaneous disease","volume":"9","author":"Baker","year":"2020","journal-title":"F1000research"},{"key":"2026072914075819600_cit12","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s12943-021-01487-4","article-title":"Strategies to overcome\nthe main challenges of the use of CRISPR\/Cas9 as a replacement for\ncancer therapy","volume":"21","author":"Rasul","year":"2022","journal-title":"Mol. Cancer"},{"key":"2026072914075819600_cit13","doi-asserted-by":"publisher","first-page":"1259435","DOI":"10.3389\/fchem.2023.1259435","article-title":"Biomaterials-mediated CRISPR\/Cas9\ndelivery: recent\nchallenges and opportunities in gene therapy","volume":"11","author":"Dubey","year":"2023","journal-title":"Front. Chem."},{"key":"2026072914075819600_cit14","doi-asserted-by":"publisher","first-page":"2585","DOI":"10.1016\/j.ymthe.2017.08.015","article-title":"Cut and Paste: Efficient\nHomology-Directed Repair of a Dominant Negative KRT14 Mutation via\nCRISPR\/Cas9 Nickases","volume":"25","author":"Kocher","year":"2017","journal-title":"Mol. Ther."},{"key":"2026072914075819600_cit15","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.omtn.2018.05.005","article-title":"CRISPR\/Cas9-Mediated\nTreatment Ameliorates the Phenotype of the Epidermolytic Palmoplantar\nKeratoderma-like Mouse","volume":"12","author":"Luan","year":"2018","journal-title":"Molecular Therapy. Nucleic\nAcids"},{"key":"2026072914075819600_cit16","doi-asserted-by":"publisher","first-page":"2510","DOI":"10.1016\/j.apsb.2022.12.013","article-title":"Intelligent nanotherapeutic\nstrategies for the delivery of CRISPR system","volume":"13","author":"Chen","year":"2023","journal-title":"Acta Pharm. Sin. 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Mater."},{"key":"2026072914075819600_cit20","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe2888","article-title":"Microneedle-assisted genome editing: A transdermal\nstrategy of targeting NLRP3 by CRISPR-Cas9 for synergistic therapy\nof inflammatory skin disorders","volume":"7","author":"Wan","year":"2021","journal-title":"Sci. Adv."},{"key":"2026072914075819600_cit21","doi-asserted-by":"publisher","first-page":"7634","DOI":"10.1039\/D2TB00645F","article-title":"Cationic lipopolymeric\nnanoplexes containing the CRISPR\/Cas9\nribonucleoprotein for genome surgery","volume":"10","author":"Sahel","year":"2022","journal-title":"J. Mater.\nChem. 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Pharm."},{"key":"2026072914075819600_cit32","doi-asserted-by":"publisher","first-page":"837","DOI":"10.3390\/PHARMACEUTICS12090837","article-title":"Recent Advances\nin Nanocarrier-Assisted Therapeutics\nDelivery Systems","volume":"12","author":"Su","year":"2020","journal-title":"Pharmaceutics"},{"key":"2026072914075819600_cit33","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.3390\/PHARMACEUTICS15051502","article-title":"Cationic Polymers as Transfection\nReagents for Nucleic Acid Delivery","volume":"15","author":"Cai","year":"2023","journal-title":"Pharmaceutics"},{"key":"2026072914075819600_cit34","doi-asserted-by":"publisher","first-page":"57","DOI":"10.3390\/PHARMACEUTICS10020057","article-title":"Impact of Particle Size and Polydispersity Index on\nthe Clinical Applications of Lipidic Nanocarrier Systems","volume":"10","author":"Danaei","year":"2018","journal-title":"Pharmaceutics"}],"container-title":["ACS Applied Bio Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsabm.5c01478","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aabmcb\/article-pdf\/8\/11\/10137\/66302074\/acsabm.5c01478.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aabmcb\/article-pdf\/8\/11\/10137\/66302074\/acsabm.5c01478.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T18:14:08Z","timestamp":1785348848000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aabmcb\/article\/8\/11\/10137\/5235171\/Lipopolymeric-Nanoplex-Mediated-CRISPR-Cas9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,31]]},"references-count":34,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,10,31]]},"published-print":{"date-parts":[[2025,11,17]]}},"URL":"https:\/\/doi.org\/10.1021\/acsabm.5c01478","relation":{},"ISSN":["2576-6422"],"issn-type":[{"value":"2576-6422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,31]]}}}