{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:32:58Z","timestamp":1783423978153,"version":"3.54.6"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"sterna biologicals GmbH"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Augmented mucosal expression of the transcription factor GATA3 has been implicated in the pathogenesis of ulcerative colitis (UC). Here, we evaluated the efficacy and safety of SB012, an enema formulation of the DNAzyme hgd40 that specifically inactivates GATA3 messenger RNA, for induction therapy in patients with active UC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>In this randomized, double-blind, placebo-controlled, multicenter, phase 2a study, patients with moderately-to-severely active UC were randomized to either receive SB012 enema (225\u2009mg hgd40) or placebo once daily for 4\u2009weeks. The primary endpoint was change in the Total Mayo Score at week 4 compared to baseline values in the SB012 versus placebo group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients were randomized 2:1 to the SB012 (n\u2009=\u200913) or placebo (n\u2009=\u20097) group. The treatment difference between the SB012 and placebo group was not statistically significant at week 4 (P\u2009=\u2009.286). In patients not treated with glucocorticoids, the Total Mayo score in the SB012 group improved on day 28 by \u22122.2 (P\u2009=\u2009.027; 95%CI: \u22124.1 to \u22120.3) compared to placebo, whereas no improvement was seen in patients using corticosteroids. Further, the median Total Mayo Score in the SB012 group dropped significantly from 9.0 (Q1-Q3 6.5-10) at baseline to 7.0 (4.0-8.5) at week 4 (P\u2009=\u2009.004), while there were no significant changes in the placebo group. Endoscopic improvement was reached by 17% (2\/12) and 57% (4\/7) in the SB012 and 17% (1\/6) and 50% (3\/6) in the placebo group at weeks 4 (P\u2009=\u20091.0) and 8 (P\u2009=\u20091.0), respectively. SB012 application was well tolerated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, topical application of the GATA3-specific DNAzyme formulation SB012 was well tolerated, but did not reach the defined primary endpoint of treatment difference at week 4 between the SB012 and placebo group in active moderate-to-severe UC patients, unless confounding by glucocorticoids was taken into account.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ibd\/izag046","type":"journal-article","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T11:42:46Z","timestamp":1778326966000},"page":"1354-1365","source":"Crossref","is-referenced-by-count":2,"title":["Targeting the transcription factor GATA3 by the DNAzyme formulation SB012 in patients with moderately-to-severely active ulcerative colitis: a multicenter, randomized, placebo-controlled, phase 2a induction trial"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8556-8433","authenticated-orcid":false,"given":"Raja","family":"Atreya","sequence":"first","affiliation":[{"name":"Medical Department 1, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen,","place":["Germany"]},{"name":"Deutsches Zentrum Immuntherapie, DZI, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"K\u00fchbacher","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/Gastroenterology, Asklepios Westklinikum , Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Vieth","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Pathologie, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, Klinikum Bayreuth , Bayreuth,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Jefremow","sequence":"additional","affiliation":[{"name":"Medical Department 1, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen,","place":["Germany"]},{"name":"Deutsches Zentrum Immuntherapie, DZI, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Hirschmann","sequence":"additional","affiliation":[{"name":"Medical Department 1, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen,","place":["Germany"]},{"name":"Deutsches Zentrum Immuntherapie, DZI, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian J","family":"Waldner","sequence":"additional","affiliation":[{"name":"Medical Department 1, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen,","place":["Germany"]},{"name":"Deutsches Zentrum Immuntherapie, DZI, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Fischer","sequence":"additional","affiliation":[{"name":"Medical Department 1, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen,","place":["Germany"]},{"name":"Deutsches Zentrum Immuntherapie, DZI, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"Vetter","sequence":"additional","affiliation":[{"name":"Medical Department 1, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen,","place":["Germany"]},{"name":"Deutsches Zentrum Immuntherapie, DZI, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Drvarov","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\/Gastroenterology, Asklepios Westklinikum , Hamburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2398-0844","authenticated-orcid":false,"given":"Benno","family":"Weigmann","sequence":"additional","affiliation":[{"name":"Medical Department 1, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen,","place":["Germany"]},{"name":"Deutsches Zentrum Immuntherapie, DZI, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Meyer","sequence":"additional","affiliation":[{"name":"MBC-Statistik , Falkensee,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"M\u00fchl","sequence":"additional","affiliation":[{"name":"sterna biologicals GmbH , Marburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Homburg","sequence":"additional","affiliation":[{"name":"sterna biologicals GmbH , Marburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Sarigiannis","sequence":"additional","affiliation":[{"name":"sterna biologicals GmbH , Marburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Garn","sequence":"additional","affiliation":[{"name":"Translational Inflammation Research Division & Core Facility for Single Cell Multiomics, Philipps University of Marburg \u2013 Medical Faculty, Member of the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center , Marburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Renz","sequence":"additional","affiliation":[{"name":"sterna biologicals GmbH , Marburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4344-1474","authenticated-orcid":false,"given":"Markus F","family":"Neurath","sequence":"additional","affiliation":[{"name":"Medical Department 1, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen,","place":["Germany"]},{"name":"Deutsches Zentrum Immuntherapie, DZI, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg , Erlangen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"2026070620112058400_izag046-B1","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1093\/ecco-jcc\/jjab178","article-title":"ECCO guidelines on therapeutics in ulcerative colitis: medical treatment","volume":"16","author":"Raine","year":"2022","journal-title":"J Crohns Colitis"},{"key":"2026070620112058400_izag046-B2","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/S0140-6736(23)00966-2","article-title":"Ulcerative colitis","volume":"402","author":"Le Berre","year":"2023","journal-title":"Lancet"},{"key":"2026070620112058400_izag046-B3","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1159\/000530983","article-title":"Current and emerging targeted therapies for ulcerative colitis","volume":"39","author":"Pietschner","year":"2023","journal-title":"Visc Med"},{"key":"2026070620112058400_izag046-B4","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/S2468-1253(21)00065-0","article-title":"Breaking the therapeutic ceiling in drug development in ulcerative colitis","volume":"6","author":"Alsoud","year":"2021","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2026070620112058400_izag046-B5","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1053\/j.gastro.2021.09.078","article-title":"Breaking through the therapeutic ceiling: what will it take?","volume":"162","author":"Raine","year":"2022","journal-title":"Gastroenterology"},{"key":"2026070620112058400_izag046-B6","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1016\/S2468-1253(18)30265-6","article-title":"Mechanisms of molecular resistance and predictors of response to biological therapy in inflammatory bowel disease","volume":"3","author":"Atreya","year":"2018","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2026070620112058400_izag046-B7","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/s41577-024-01008-6","article-title":"Strategies for targeting cytokines in inflammatory bowel disease","volume":"24","author":"Neurath","year":"2024","journal-title":"Nat Rev Immunol"},{"key":"2026070620112058400_izag046-B8","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/s0092-8674(00)80240-8","article-title":"The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells","volume":"89","author":"Zheng","year":"1997","journal-title":"Cell"},{"key":"2026070620112058400_izag046-B9","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1538\/expanim.63.133","article-title":"Overexpression of GATA-3 in T cells accelerates dextran sulfate sodium-induced colitis","volume":"63","author":"Okamura","year":"2014","journal-title":"Exp Anim"},{"key":"2026070620112058400_izag046-B10","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1053\/j.gastro.2016.09.005","article-title":"Rectal delivery of a DNAzyme that specifically blocks the transcription factor GATA3 and reduces colitis in mice","volume":"152","author":"Popp","year":"2017","journal-title":"Gastroenterology"},{"key":"2026070620112058400_izag046-B11","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1097\/MIB.0b013e3182802b0e","article-title":"Predictors of endoscopic inflammation in patients with ulcerative colitis in clinical remission","volume":"19","author":"Rosenberg","year":"2013","journal-title":"Inflamm Bowel Dis"},{"key":"2026070620112058400_izag046-B12","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1111\/j.1442-200X.2009.03019.x","article-title":"Increased mucosal expression of GATA-3 and STAT-4 in pediatric ulcerative colitis","volume":"52","author":"Ohtani","year":"2010","journal-title":"Pediatr Int"},{"key":"2026070620112058400_izag046-B13","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1097\/MIB.0000000000000811","article-title":"Profiles of lamina propria T helper cell subsets discriminate between ulcerative colitis and Crohn\u2019s disease","volume":"22","author":"Li","year":"2016","journal-title":"Inflamm Bowel Dis"},{"key":"2026070620112058400_izag046-B14","doi-asserted-by":"publisher","first-page":"13330","DOI":"10.1021\/bi9812221","article-title":"Mechanism and utility of an RNA-cleaving DNA enzyme","volume":"37","author":"Santoro","year":"1998","journal-title":"Biochemistry"},{"key":"2026070620112058400_izag046-B15","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.2353\/ajpath.2007.070120","article-title":"Brothers in arms: DNA enzymes, short interfering RNA, and the emerging wave of small-molecule nucleic acid-based gene-silencing strategies","volume":"171","author":"Bhindi","year":"2007","journal-title":"Am J Pathol"},{"key":"2026070620112058400_izag046-B16","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.1056\/NEJM198712243172603","article-title":"Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study","volume":"317","author":"Schroeder","year":"1987","journal-title":"N Engl J Med"},{"key":"2026070620112058400_izag046-B17","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1016\/0016-5085(88)90677-4","article-title":"Comparison of delayed-release 5-aminosalicylic acid (mesalazine) and sulfasalazine as maintenance treatment for patients with ulcerative colitis","volume":"94","author":"Riley","year":"1988","journal-title":"Gastroenterology"},{"key":"2026070620112058400_izag046-B18","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1111\/apt.16626","article-title":"Agreement between local and central reading of endoscopic disease activity in ulcerative colitis: results from the tofacitinib OCTAVE trials","volume":"54","author":"Feagan","year":"2021","journal-title":"Aliment Pharmacol Ther"},{"key":"2026070620112058400_izag046-B19","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.japna.2003.07.002","article-title":"Development and validation of a sensitive, specific, and rapid hybridization-ELISA assay for determination of concentrations of a ribozyme in biological matrices","volume":"34","author":"Brown-Augsburger","year":"2004","journal-title":"J Pharm Biomed Anal"},{"key":"2026070620112058400_izag046-B20","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1056\/NEJMoa1900750","article-title":"Ustekinumab as induction and maintenance therapy for ulcerative colitis","volume":"381","author":"Sands","year":"2019","journal-title":"N Engl J Med"},{"key":"2026070620112058400_izag046-B21","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1056\/NEJMoa1606910","article-title":"Tofacitinib as induction and maintenance therapy for ulcerative colitis","volume":"376","author":"Sandborn","year":"2017","journal-title":"N Engl J Med"},{"key":"2026070620112058400_izag046-B22","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1136\/gut.2010.221127","article-title":"Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial","volume":"60","author":"Reinisch","year":"2011","journal-title":"Gut"},{"key":"2026070620112058400_izag046-B23","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1093\/ecco-jcc\/jjad162","article-title":"Submucosal injection of the RNA oligonucleotide GUT-1 in active ulcerative colitis patients: a randomized, double-blind, placebo-controlled phase 2a induction trial","volume":"18","author":"Atreya","year":"2024","journal-title":"J Crohns Colitis"},{"key":"2026070620112058400_izag046-B24","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1016\/S2468-1253(20)30301-0","article-title":"Cobitolimod for moderate-to-severe, left-sided ulcerative colitis (CONDUCT): a phase 2b randomised, double-blind, placebo-controlled, dose-ranging induction trial","volume":"5","author":"Atreya","year":"2020","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2026070620112058400_izag046-B25","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/nm.4046","article-title":"Transient inhibition of ROR-\u03b3t therapeutically limits intestinal inflammation by reducing TH17 cells and preserving group 3 innate lymphoid cells","volume":"22","author":"Withers","year":"2016","journal-title":"Nat Med"},{"key":"2026070620112058400_izag046-B26","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.3389\/fimmu.2018.02307","article-title":"An ROR\u03b3t oral inhibitor modulates IL-17 responses in peripheral blood and intestinal mucosa of Crohn\u2019s disease patients","volume":"9","author":"Bassolas-Molina","year":"2018","journal-title":"Front Immunol"},{"key":"2026070620112058400_izag046-B27","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1038\/ni.1677","article-title":"IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells","volume":"9","author":"Dardalhon","year":"2008","journal-title":"Nat Immunol"},{"key":"2026070620112058400_izag046-B28","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1136\/gutjnl-2013-305947","article-title":"IL-9 and its receptor are predominantly involved in the pathogenesis of UC","volume":"64","author":"Nalleweg","year":"2015","journal-title":"Gut"},{"key":"2026070620112058400_izag046-B29","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/ni.2920","article-title":"TH9 cells that express the transcription factor PU.1 drive T cell-mediated colitis via IL-9 receptor signaling in intestinal epithelial cells","volume":"15","author":"Gerlach","year":"2014","journal-title":"Nat Immunol"},{"key":"2026070620112058400_izag046-B30","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1002\/eji.201948430","article-title":"IL-9 exerts biological function on antigen-experienced murine T cells and exacerbates colitis induced by adoptive transfer","volume":"50","author":"de Heusch","year":"2020","journal-title":"Eur J Immunol"},{"key":"2026070620112058400_izag046-B31","doi-asserted-by":"publisher","first-page":"1987","DOI":"10.1056\/NEJMoa1411776","article-title":"Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme","volume":"372","author":"Krug","year":"2015","journal-title":"N Engl J Med"}],"container-title":["Inflammatory Bowel Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article-pdf\/32\/7\/1354\/68273812\/izag046.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article-pdf\/32\/7\/1354\/68273812\/izag046.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:11:41Z","timestamp":1783383101000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ibdjournal\/article\/32\/7\/1354\/8676551"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,12]]},"references-count":31,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,5,12]]},"published-print":{"date-parts":[[2026,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ibd\/izag046","relation":{},"ISSN":["1078-0998","1536-4844"],"issn-type":[{"value":"1078-0998","type":"print"},{"value":"1536-4844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7]]},"published":{"date-parts":[[2026,5,12]]}}}