Giacomo Roman

• Roman, Giacomo; Lauritzen, Knut Husø; Harrison, Sean Philip; Bhattacharya, Anindita; Andresen, Marianne Seierstad & Mowinckel, Marie-Christine [Show all 16 contributors for this article] (2025). Ex vivo correction of severe coagulation Factor VII deficiency in patient-derived 3D liver organoids. Haematologica. ISSN 0390-6078. doi: 10.3324/haematol.2025.288046. Full text in Research Archive Show summary

  Coagulation factor (F) VII deficiency is the most frequent among the rare, inherited bleeding disorders and is predominantly caused by missense mutations in the F7 gene. The disease phenotype ranges from asymptomatic cases to extremely severe hemorrhagic forms, requiring prophylactic injections with plasma-derived or recombinant FVII concentrates. In response, we have developed an autologous cell-based approach that corrects the disease-causing mutation in patient-derived induced pluripotent stem cells (iPSCs) and generates therapeutic, three-dimensional hepatic organoids (HOs). We report the CRISPRmediated correction of homozygous c.718G>C (p.G240R), a missense mutation associated with a severe, life-threatening bleeding phenotype. The HOs contain all liver cell types and exhibit key liver functions, including coagulation factor production. After correction, our data indicate that the patient-derived HOs secrete consistent amounts of functional FVII protein, resulting in improved thrombin generation times. These results represent a significant milestone toward the establishment of an autologous cell-based therapy for patients with FVII- and other coagulation factor deficiencies.

• Roman, Giacomo; Stavik, Benedicte; Lauritzen, Knut Husø; Sandset, Per Morten; Harrison, Sean & Sullivan, Gareth John [Show all 7 contributors for this article] (2023). “iPSC-derived liver organoids and inherited bleeding disorders: Potential and future perspectives”. Frontiers in Physiology. 14. doi: 10.3389/fphys.2023.1094249. Full text in Research Archive Show summary

  The bleeding phenotype of hereditary coagulation disorders is caused by the low or undetectable activity of the proteins involved in hemostasis, due to a broad spectrum of genetic alterations. Most of the affected coagulation factors are produced in the liver. Therefore, two-dimensional (2D) cultures of primary human hepatocytes and recombinant overexpression of the factors in non-human cell lines have been primarily used to mimic disease pathogenesis and as a model for innovative therapeutic strategies. However, neither human nor animal cells fully represent the hepatocellular biology and do not harbor the exact genetic background of the patient. As a result, the inability of the current in vitro models in recapitulating the in vivo situation has limited the studies of these inherited coagulation disorders. Induced Pluripotent Stem Cell (iPSC) technology offers a possible solution to overcome these limitations by reprogramming patient somatic cells into an embryonic-like pluripotent state, thus giving the possibility of generating an unlimited number of liver cells needed for modeling or therapeutic purposes. By combining this potential and the recent advances in the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology, it allows for the generation of autologous and gene corrected liver cells in the form of three-dimensional (3D) liver organoids. The organoids recapitulate cellular composition and organization of the liver, providing a more physiological model to study the biology of coagulation proteins and modeling hereditary coagulation disorders. This advanced methodology can pave the way for the development of cell-based therapeutic approaches to treat inherited coagulation disorders. In this review we will explore the use of liver organoids as a state-of-the-art methodology for modeling coagulation factors disorders and the possibilities of using organoid technology to treat the disease.

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• Dugarte, Maria Eugenia Chollet; Bhattacharya, Anindita; Roman, Giacomo; Harrison, Sean Philip; Baumgarten, Saphira Felicitas & Andersen, Elisabeth [Show all 12 contributors for this article] (2025). Autologous gene-corrected hepatic organoids for the treatment of FVII deficiency. Research and Practice in Thrombosis and Haemostasis (RPTH). 9(S2), p. 265–266. doi: 10.1016/j.rpth.2025.102925. Full text in Research Archive
• Roman, Giacomo; Lauritzen, Knut Husø; Harrison, Sean Philip; Bhattacharya, Anindita; Mowinckel, Marie-Christine & Andresen, Marianne Seierstad [Show all 14 contributors for this article] (2025). Gene editing in patient-derived iPSCs restores coagulation FVII deficiency in 3D liver organoids. Research and Practice in Thrombosis and Haemostasis (RPTH). 9(S2), p. 950–951. doi: 10.1016/j.rpth.2025.102923. Full text in Research Archive
• Bhattacharya, Anindita; Roman, Giacomo; Harrison, Sean Philip; Sullivan, Gareth John; Mowinckel, Marie-Christine & Sandset, Per Morten [Show all 10 contributors for this article] (2024). Developing cell-based genome editing approach for antithrombin deficiency: a therapeutic prospect. Research and Practice in Thrombosis and Haemostasis (RPTH). doi: 10.1016/j.rpth.2024.102504. Full text in Research Archive
• Dugarte, Maria Eugenia Chollet; Bhattacharya, Anindita; Roman, Giacomo; Harrison, Sean; Baumgarten, Saphira Felicitas & Andersen, Elisabeth [Show all 12 contributors for this article] (2024). Autologous gene-corrected stem cell-derived hepatic organoids for the treatment of FVII deficiency. HemaSphere. doi: 10.1002/hem3.104. Full text in Research Archive
• Dugarte, Maria Eugenia Chollet; Andersen, Elisabeth; Harrison, Sean Philip; Morena-Barrio, Maria Eugenia de la; Baumgarten, Saphira Felicitas & Bhattacharya, Anindita [Show all 14 contributors for this article] (2023). OC 07.5 Modeling and Correcting FVII Deficiency using Human Stem Cell-Derived Hepatic Organoids. Research and Practice in Thrombosis and Haemostasis (RPTH). 7(Oral communications ISTH 2023). doi: 10.1016/j.rpth.2023.100470. Full text in Research Archive
• Roman, Giacomo; Lauritzen, Knut Husø; Harrison, Sean Philip; Sullivan, Gareth John; Iversen, Nina & Henriksson, Carola Elisabeth [Show all 10 contributors for this article] (2023). OC 07.1 Autologous CRISPR/Cas9 Correction of a Missense Variant from a Patient with Severe, Inherited FVII Deficiency. Research and Practice in Thrombosis and Haemostasis (RPTH). 7(Oral communications ISTH 2023). doi: 10.1016/j.rpth.2023.100475. Full text in Research Archive
• Roman, Giacomo; Lauritzen, Knut Husø; Harrison, Sean; Sullivan, Gareth John; Iversen, Nina & Henriksson, Carola Elisabeth [Show all 10 contributors for this article] (2023). Autologous CRISPR/Cas9 correction of a missense variant from a patient with severe, inherited FVII deficiency. Full text in Research Archive
• Roman, Giacomo; Lauritzen, Knut Husø; Harrison, Sean Philip; Sullivan, Gareth John; Iversen, Nina & Henriksson, Carola Elisabeth [Show all 10 contributors for this article] (2023). OC 07.1 Autologous CRISPR/Cas9 Correction of a Missense Variant from a Patient with Severe, Inherited FVII Deficiency. Research and Practice in Thrombosis and Haemostasis (RPTH). doi: 10.1016/j.rpth.2023.100475. Full text in Research Archive

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