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 language | English |
|---|---|
| Pages (from-to) | 251-262 |
| Number of pages | 12 |
| Journal | Human Gene Therapy |
| Volume | 15 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2004 |
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ASJC Scopus subject areas
- Genetics
Cite this
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. / 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.
In: Human Gene Therapy, Vol. 15, No. 3, 01.03.2004, p. 251-262.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Anti-human immunodeficiency virus hematopoietic progenitor cell-delivered ribozyme in a phase I study
T2 - Myeloid and lymphoid reconstitution in human immunodeficiency virus type-1-infected patients
AU - Amado, Rafael G.
AU - Mitsuyasu, Ronald T.
AU - Rosenblatt, Joseph D
AU - Ngok, Frances K.
AU - Bakker, Andreas
AU - Cole, Steve
AU - Chorn, Nathalie
AU - Lin, Lii Shin
AU - Bristol, Gregory
AU - Boyd, Maureen P.
AU - Macpherson, Janet L.
AU - Fanning, Gregory C.
AU - Todd, Alison V.
AU - Ely, Julie A.
AU - Zack, Jerome A.
AU - Symonds, Geoff P.
PY - 2004/3/1
Y1 - 2004/3/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=12144291445&partnerID=8YFLogxK
U2 - 10.1089/104303404322886101
DO - 10.1089/104303404322886101
M3 - Article
VL - 15
SP - 251
EP - 262
JO - Human Gene Therapy
JF - Human Gene Therapy
SN - 1043-0342
IS - 3
ER -