A clinical trial of retroviral-mediated transfer of a rev-responsive element decoy gene into CD34(+) cells from the bone marrow of human immunodeficiency virus-1-infected children.
Genetic modification of hematopoietic stem cells with genes that inhibit replication of human immunodeficiency virus-1 (HIV-1) could lead to development of T lymphocytes and monocytic cells resistant to HIV-1 infection after transplantation. We performed a clinical trial to evaluate the safety and feasibility of this procedure, using bone marrow from four HIV-1-infected pediatric subjects (ages 8 to 17 years). We obtained bone marrow, isolated CD34(+) cells, performed in vitro transduction with a retroviral vector carrying a rev-responsive element (RRE) decoy gene, and reinfused the cells into these subjects with no evidence of adverse effects. The levels of gene-containing leukocytes in peripheral blood samples in the 1 year after gene transfer/cell infusion have been extremely low. These observations support the potential of performing gene therapy for HIV-1 using hematopoietic cells, but emphasize the need for improved gene transfer techniques.
Kohn
D B
DB
Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, CA 90027, USA. dkohn@chla.usc.edu
Bauer
G
G
Rice
C R
CR
Rothschild
J C
JC
Carbonaro
D A
DA
Valdez
P
P
Hao
Q l
Ql
Zhou
C
C
Bahner
I
I
Kearns
K
K
Brody
K
K
Fox
S
S
Haden
E
E
Wilson
K
K
Salata
C
C
Dolan
C
C
Wetter
C
C
Aguilar-Cordova
E
E
Church
J
J
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000293:Adolescent; D002454:Cell Differentiation; D002648:Child; D018014:Gene Transfer Techniques; D015757:Genes, rev; D015316:Genetic Therapy; D005822:Genetic Vectors; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology; D006801:Humans; D010865:Pilot Projects; D012190:Retroviridae; D013601:T-Lymphocytes / Q000276:immunology; D014779:Virus Replication / Q000235:genetics*