1/3/2024 0 Comments Gene therapy for scid![]() Update on primary immunodeficiency diseases. Updated August 21, 2006.īonilla FA, Geha RS. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. 117(5):1270-81.Ĭavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, et al. Homeostatically proliferating CD4 T cells are involved in the pathogenesis of an Omenn syndrome murine model. Khiong K, Murakami M, Kitabayashi C, et al. Gene therapy for severe combined immunodeficiency: are we there yet?. Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders. Stray-Pedersen A, Sorte HS, Samarakoon P, Gambin T, Chinn IK, et. BM, bone marrow FSC, forward scatter FV, foamy viral FV-PGK-mCherry-γC, FV expressing mCherry and γC under human phosphoglycerate kinase promoter HSPC, hematopoietic stem and progenitor cell PB, peripheral blood SSC, side scatter TREC, T cell receptor excision circle.Justiz Vaillant AA, Mohseni M. HSPCs were defined as CD45 +CD34 + cells from BM. Scatter was defined based on forward scatter (FSC) and side scatter (SSC) profile. (E) Colony forming potential of mCherry + HSPCs, which shows transduction of stem cells by FV vector. (C) TRECs in PB of H867 (D) colony forming potential of BM CD34 + HSPCs in comparison with healthy dog 3.5 years postviral vector injection. (B) Kinetics of CD3 + cell reconstitution (based on CD3 + cells per microliter of blood) in H867. Lymphocyte population was defined based on forward and side scatter. (A) Kinetics of gene marking based on fluorophore expression in PB lymphocytes from H867 treated with FV-PGK-mCherry-γC. Long-term immune restoration in T cell immunity and in situ transduction of BM CD34 + HSPCs. SCID-X1 canine animal model hematopoietic stem cells in vivo gene therapy lentiviral vector severe combined immunodeficiency stem cell mobilization. Since manufacturing of cocal LV is similar to VSV-G LV, this approach is easily translatable to a clinical setting, thus providing for a highly portable and accessible gene therapy platform for SCID-X1. These data demonstrate that clinically relevant and durable correction of canine SCID-X1 can be achieved with in vivo delivery of cocal LV. Comparative analysis of integration profiles of foamy viral (FV) vector and cocal LV vector after in vivo gene therapy found distinct integration-site patterns. Retroviral integration-site analysis demonstrated polyclonal T cell reconstitution. Therapeutic levels of gene-corrected CD3 + T cells were demonstrated for at least 16 months, and all other correlates of T cell functionality were within normal range. Two SCID-X1 neonatal canines treated with this approach achieved long-term therapeutic immune reconstitution with no prior conditioning. The cocal envelope is resistant to serum inactivation compared with the commonly used vesicular stomatitis virus envelope glycoprotein (VSV-G) envelope and thus well suited for systemic delivery. Here, we investigated the use of the cocal envelope to pseudotype a lentiviral (LV) vector expressing a functional gammaC gene. Considering these impediments, we have developed an in vivo gene therapy approach to treat canine SCID-X1 after HSPC mobilization and systemic delivery of the therapeutic vector. In addition, ex vivo gene therapy approaches require sophisticated facilities to manufacture gene-modified cells and to care for the patients after chemotherapy. Nevertheless, this form of treatment is associated with an increased risk of infectious disease complications and genotoxicity mainly due to the conditioning regimen. Hematopoietic stem and progenitor cell (HSPC)-based ex vivo gene therapy has demonstrated clinical success for X-linked severe combined immunodeficiency (SCID-X1) patients who lack a suitable donor for HSPC transplantation.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |