دورية
Anti-Human Immunodeficiency Virus Hematopoietic Progenitor Cell-Delivered Ribozyme in a Phase I Study: Myeloid and Lymphoid Reconstitution in Human Immunodeficiency Virus Type-1–Infected Patients
| العنوان: | Anti-Human Immunodeficiency Virus Hematopoietic Progenitor Cell-Delivered Ribozyme in a Phase I Study: Myeloid and Lymphoid Reconstitution in Human Immunodeficiency Virus Type-1–Infected Patients |
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| المؤلفون: | Amado, Rafael G., Mitsuyasu, Ronald T., Rosenblatt, Joseph D., Ngok, Frances K., Bakker, Andreas, Cole, Steve, Chorn, Nathalie, Lin, Lii-Shin, Bristol, Gregory, Boyd, Maureen P., MacPherson, Janet L., Fanning, Gregory C., Todd, Alison V., Ely, Julie A., Zack, Jerome A., Symonds, Geoff P. |
| المصدر: | Human Gene Therapy; March 01, 2004, Vol. 15 Issue: 3 p251-262, 12p |
| مستخلص: | A phase I gene transfer clinical study was undertaken to examine the ability to introduce a potential anti-human immunodeficiency virus (HIV) gene therapeutic into hematopoietic progenitor cells (HPC), thereby contributing to multilineage engraftment. The potential therapeutic effect of genetically modifying HPC with protective genes in HIV-infected adults depends in part on the presence of adult thymic activity and myeloid capacity in the setting of HIV replication. Herein we report the presence and expression of a retroviral vector encoding an anti-HIV-1 ribozyme in mature hematopoietic cells of different lineages, and de novo T-lymphocyte development ensuing from genetically engineered CD34+ HPC. Sustained output of vector-containing mature myeloid and T-lymphoid cells was detected even in patients with multidrug-resistant infection. In addition, the study showed that the degree of persistence of gene-containing cells was dependent on transduced HPC dose. These novel findings support the concept of gene therapy as a modality to effect immune reconstitution with cells engineered to inhibit HIV replication and this report represents the first demonstration of long-term maintenance of a potential therapeutic transgene in HIV disease. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 10430342 15577422 |
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| DOI: | 10.1089/104303404322886101 |