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.
|Title||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.|
|Publication Type||Journal Article|
|Year of Publication||2004|
|Authors||Amado RG, Mitsuyasu RT, Rosenblatt JD, Ngok FK, Bakker A, Cole S, Chorn N, Lin L-S, Bristol G, Boyd MP, MacPherson JL, Fanning GC, Todd AV, Ely JA, Zack JA, Symonds GP|
|Journal||Hum Gene Ther|
|Date Published||2004 Mar|
|Keywords||Adult, Anti-HIV Agents, Antigens, CD34, CD4-Positive T-Lymphocytes, Female, Gene Expression, Gene Transfer Techniques, Genetic Therapy, Genetic Vectors, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, HIV Infections, HIV-1, Humans, Lymphocytes, Male, Middle Aged, Myeloid Cells, Polymerase Chain Reaction, Retroviridae, RNA, Catalytic|
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.
|Alternate Journal||Hum. Gene Ther.|
|Grant List||AI01662 / AI / NIAID NIH HHS / United States |
AI27660 / AI / NIAID NIH HHS / United States
AI28697 / AI / NIAID NIH HHS / United States
CA70080 / CA / NCI NIH HHS / United States
M01-RR-00865 / RR / NCRR NIH HHS / United States