{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:55:53Z","timestamp":1791035753408,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>This study evaluated the safety, tolerability, and pharmacokinetics of LEM\u2010S401, a novel siRNA therapeutic with DegradaBALL, a mesoporous silica nanoparticle\u2010based delivery system. LEM\u2010S401 is designed to deliver siRNA targeting connective tissue growth factor (CTGF) to fibroblasts for treating hypertrophic scars and keloids, both of which result from abnormal collagen proliferation. LEM\u2010S401, containing unmodified siRNA LEM\u201017234 encapsulated in DegradaBALL nanoparticles, was administered subcutaneously to healthy adults in a randomized, double\u2010blind, placebo\u2010controlled, single\u2010ascending dose study. Safety and tolerability assessments included vital signs, adverse events (AEs), laboratory tests, and cytokine levels. Pharmacokinetic analysis of LEM\u201017234 and silicon (Si), the primary component of DegradaBALL, was performed using blood samples collected at specified time points. LEM\u2010S401 demonstrated a favorable safety and tolerability profile with only mild, self\u2010resolving injection site reactions including pain and erythema. No systemic AEs were observed, and cytokine levels showed no significant changes between the treatment and placebo groups. Pharmacokinetic analysis revealed that LEM\u201017234 was below the plasma detection limit, indicating no notable systemic exposure of siRNA, while Si showed no dose\u2010dependent systemic exposure, suggesting minimal systemic circulation of the mesoporous silica nanoparticles. These findings suggest DegradaBALL effectively encapsulates and delivers siRNA locally without significant systemic exposure. The novel DegradaBALL delivery system enables the stable and targeted delivery of siRNA, which presumably overcomes challenges related to siRNA instability and off\u2010target effects. LEM\u2010S401 has the potential to advance the treatment of fibrotic skin diseases such as keloids and hypertrophic scars by delivering siRNA directly to fibroblasts, thereby inhibiting excessive collagen production.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                    identifier: NCT04707131.\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04707131?cond=NCT04707131&amp;rank=1\">https:\/\/clinicaltrials.gov\/study\/NCT04707131?cond=NCT04707131&amp;rank=1<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1111\/cts.70207","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T05:15:10Z","timestamp":1743484510000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A First\u2010In\u2010Human Phase 1 Study to Evaluate the Safety and Tolerability of\n                    <scp>LEM<\/scp>\n                    \u2010\n                    <scp>S401<\/scp>\n                    , a Novel\n                    <scp>siRNA<\/scp>\n                    \u2010\n                    <scp>DegradaBALL<\/scp>\n                    Drug Targeting\n                    <scp>CTGF<\/scp>\n                    in Healthy Adults"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7964-8728","authenticated-orcid":false,"given":"Ha\u2010Yeon","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology ChungBuk National University College of Medicine  Cheongju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2479-3856","authenticated-orcid":false,"given":"Jaeso","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Seoul National University Bundang Hospital  Seongnam Republic of Korea"},{"name":"Institute of Biotherapeutics Convergence Technology, Lemonex Inc.  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9851-7555","authenticated-orcid":false,"given":"Min Kyu","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics ChungBuk National University College of Medicine and Hospital  Cheongju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8623-6716","authenticated-orcid":false,"given":"Dal\u2010Hee","family":"Min","sequence":"additional","affiliation":[{"name":"Institute of Biotherapeutics Convergence Technology, Lemonex Inc.  Seoul Republic of Korea"},{"name":"Department of Chemistry Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0965-0531","authenticated-orcid":false,"given":"Jun Gi","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics ChungBuk National University College of Medicine and Hospital  Cheongju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4844-1070","authenticated-orcid":false,"given":"Cheolhee","family":"Won","sequence":"additional","affiliation":[{"name":"Institute of Biotherapeutics Convergence Technology, Lemonex Inc.  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