{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:44:31Z","timestamp":1792021471282,"version":"4.4.0"},"reference-count":0,"publisher":"Georg Thieme Verlag KG","funder":[{"name":"Tangram therapeutics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"abstract":"<jats:p>Non-factor therapeutics have transformed the treatment paradigm in hemophilia A. Owing to their mode of action, these agents may also provide benefit for other rare bleeding disorders (RBDs) such as von Willebrand disease (VWD)-type 3 and Factor X (FX) deficiency. Targeting protein Z-dependent protease inhibitor (ZPI), a natural anticoagulant, is a novel strategy to enhance hemostasis. We evaluated the effects of ZPI post-transcriptional silencing using a GalNAc-conjugated siRNA (mTGM-148) in von Willebrand factor-deficient (VwfKO) mice and in mice with strongly reduced factor X levels (&lt; 1%; f10low-mice). mTGM-148 reduced plasma ZPI antigen below 15% in both models. In VwfKO-mice, mTGM-148 significantly enhanced contact activation-initiated thrombin generation and normalized INTEM clotting parameters. In f10low-mice, thrombin generation was minimally affected, but EXTEM clotting parameters were significantly ameliorated. Importantly, mTGM-148 treatment significantly reduced blood loss in the tail clip model for both VwfKO-mice and f10low-mice. These data suggest that ZPI post-transcriptional silencing is a viable strategy to improve the hemostatic potential in both VWD-type 3 and FX deficiency. As such, ZPI inhibition represents a promising non-factor therapeutic approach for selected RBDs.<\/jats:p>","DOI":"10.1055\/a-2979-5643","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:46:31Z","timestamp":1792017991000},"source":"Crossref","is-referenced-by-count":0,"title":["Small interfering RNA targeting protein Z-dependent protease inhibitor improves hemostasis in Von Willebrand factor- and Factor X-deficient mice"],"prefix":"10.1055","author":[{"given":"Rim","family":"Hamze","sequence":"additional","affiliation":[{"name":"INSERM U1176 Haemostasis Inflammation Thrombosis, \u00cele-de-France, France","place":["Le Kremlin-Bic\u00eatre"],"department":["U1176"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariem","family":"Khamari","sequence":"additional","affiliation":[{"name":"INSERM U1176 Haemostasis Inflammation Thrombosis, Ile de France, France","place":["Le Kremlin-Bicetre"],"department":["U1176"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn R","family":"Calabro","sequence":"additional","affiliation":[{"name":"Tangram therapeutics, United Kingdom of Great Britain and Northern Ireland","place":["London"],"department":["Preclinical development"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Jehl","sequence":"additional","affiliation":[{"name":"INSERM U1176 Haemostasis Inflammation Thrombosis, \u00cele-de-France, France","place":["Le Kremlin-Bic\u00eatre"],"department":["U1176"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Becker","sequence":"additional","affiliation":[{"name":"Tangram Therapeutics, United Kingdom of Great Britain and Northern Ireland","place":["London"],"department":["Preclinical development"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre J","family":"Debacker","sequence":"additional","affiliation":[{"name":"Tangram Therapeutics, United Kingdom of Great Britain and Northern Ireland","place":["London"],"department":["Preclinical development"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie W","family":"Prusell","sequence":"additional","affiliation":[{"name":"Tangram Therapeutics, United Kingdom of Great Britain and Northern Ireland","place":["London"],"department":["Preclinical development"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Elle","sequence":"additional","affiliation":[{"name":"Tangram therapeutics, United Kingdom of Great Britain and Northern Ireland","place":["London"],"department":["Preclinical development"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Pang","sequence":"additional","affiliation":[{"name":"WuXi AppTec, Switzerland","place":["Couvet"],"department":["Discovery services"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Sun","sequence":"additional","affiliation":[{"name":"WuXi AppTec, Shanghai, China","place":["Shanghai"],"department":["Discovery services"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"WuXi AppTec, Shanghai, China","place":["Shanghai"],"department":["Discovery services"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiugang","family":"Lei","sequence":"additional","affiliation":[{"name":"WuXi AppTec, Shanghai, China","place":["Shanghai"],"department":["Discovery services"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Chen","sequence":"additional","affiliation":[{"name":"WuXi AppTec, Shanghai, China","place":["Shanghai"],"department":["Discovery services"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Gu\u00e9rin","sequence":"additional","affiliation":[{"name":"INSERM U1176 Haemostasis Inflammation Thrombosis, \u00cele-de-France, France","place":["Le Kremlin-Bic\u00eatre"],"department":["U1176"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"McCluskey","sequence":"additional","affiliation":[{"name":"INSERM U1176 Haemostasis Inflammation Thrombosis, \u00cele-de-France, France","place":["Le Kremlin-Bic\u00eatre"],"department":["U1176"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8271-6795","authenticated-orcid":false,"given":"Caterina","family":"Casari","sequence":"additional","affiliation":[{"name":"INSERM, \u00cele-de-France, France","place":["Le Kremlin-Bicetre"],"department":["Unit 1176"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1370-5312","authenticated-orcid":false,"given":"Elsa P","family":"Bianchini","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Sud, France, France","place":["KREMLIN BICETRE"],"department":["UMR-S1176"]},{"name":"INSERM, France","department":["U1176"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9080-6336","authenticated-orcid":false,"given":"olivier D","family":"christophe","sequence":"additional","affiliation":[{"name":"Inserm, France, France","place":["Le Kremlin-Bicetre"],"department":["Unit 1176"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan V","family":"Whitmore","sequence":"additional","affiliation":[{"name":"Tangram Therapeutics, United Kingdom of Great Britain and Northern Ireland","place":["London"],"department":["Chief Scientific Officer"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J","family":"Lenting","sequence":"additional","affiliation":[{"name":"INSERM U1176 Haemostasis Inflammation Thrombosis, Val-de-Marne, France","place":["Le Kremlin-Bic\u00eatre"],"department":["Unit 1176"]},{"name":"INSERM, France","place":["Le Kremlin-Bicetre"],"department":["unit 1176"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecile","family":"Denis","sequence":"additional","affiliation":[{"name":"INSERM, \u00cele-de-France, France","place":["Paris"],"department":["U1176"]},{"name":"INSERM U1176 Haemostasis Inflammation Thrombosis, \u00cele-de-France, France","place":["Le Kremlin-Bic\u00eatre"],"department":["1176"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2979-5643.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:46:31Z","timestamp":1792017991000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2979-5643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,14]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1055\/a-2979-5643","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,10,14]]},"published":{"date-parts":[[2026,10,14]]}}}