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

Rafael G. Amado, Ronald T. Mitsuyasu, Joseph D Rosenblatt, Frances K. Ngok, Andreas Bakker, Steve Cole, Nathalie Chorn, Lii Shin Lin, Gregory Bristol, Maureen P. Boyd, Janet L. Macpherson, Gregory C. Fanning, Alison V. Todd, Julie A. Ely, Jerome A. Zack, Geoff P. Symonds

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112 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)251-262
Number of pages12
JournalHuman Gene Therapy
Volume15
Issue number3
DOIs
StatePublished - Mar 1 2004

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ASJC Scopus subject areas

  • Genetics

Cite this

Amado, R. G., Mitsuyasu, R. T., Rosenblatt, J. D., Ngok, F. K., Bakker, A., Cole, S., Chorn, N., Lin, L. S., Bristol, G., Boyd, M. P., Macpherson, J. L., Fanning, G. C., Todd, A. V., Ely, J. A., Zack, J. A., & Symonds, G. P. (2004). 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. Human Gene Therapy, 15(3), 251-262. https://doi.org/10.1089/104303404322886101