Transduction of Human CD34 ⁺ Cells That Mediate Long-Term Engraftment of NOD/SCID Mice by HIV Vectors

Abstract

Efficient gene transfer into human hematopoietic stem cells (HSCs) is an important goal in the study of the hematopoietic system as well as for gene therapy of hematopoietic disorders. A lentiviral vector based on the human immunodeficiency virus (HIV) was able to transduce human CD34+ cells capable of stable, long-term reconstitution of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. High-efficiency transduction occurred in the absence of cytokine stimulation and resulted in transgene expression in multiple lineages of human hematopoietic cells for up to 22 weeks after transplantation.

Influence of multiplicity of infection and protein stability on retroviral vector-mediated gene expression in hematopoietic cells

“…Similar considerations apply to the use of lentiviral vectors, which are often used at a very high MOI in preclinical models. 32,33 In the present study, transduction of murine hematopoietic cells with controlled MOI was helpful to demonstrate the substantial impact of the stability of the transgenic protein on vector performance, an issue that has not been addressed previously. A long half-life of a therapeutic protein expressed from a retroviral vector in hematopoietic cells may be of particular relevance for the correction of a large number of genetic disorders affecting long-lived mature blood cells, such as macrophages, T cells, or erythrocytes.…”

Efficient restricted gene expression in beta cells by lentivirus-mediated gene transfer into pancreatic stem/progenitor cells

“…In cell types of the haematopoietic system, mature cells have been modified by viral infection of progenitor cells that undergo differentiation. Several groups have recently reported successful transduction of reporter genes or genes of therapeutical importance into progenitor cells that were taken from umbilical cord blood or bone marrow and differentiated into mature cells [12][13][14][15]. In these experiments, the transgene was constitutively expressed, irrespective of the differentiation stage.…”

Optimization of equine infectious anemia derived vectors for hematopoietic cell lineage gene transfer

“…Vectors based on the lentivirus HIV-1 are effective in transducing human lymphocytes, 5 myeloid cells, 6 hematopoietic progenitor, 7 and NOD/SCID repopulating cells. 8 Optimization of HIV-1 vectors using self-inactivating LTRs, a variety of viral, cellular and hematopoietic cell type specific promoters, post-transcriptional elements, and insulator sequences have further improved transduction and expression of these vectors in hematopoietic cells (reviewed in Hawley 9 ).…”