Hematopoietic stem cell (HSC) therapy using replication-incompetent retroviral vectors is a promising approach to provide life-long correction for genetic defects. HSC gene therapy clinical studies have resulted in functional cures for several diseases, but in some studies clonal expansion or leukemia has occurred. This is due to the dyregulation of endogenous host gene expression from vector p...

Retroviral vector-mediated HSC gene therapy has been used to treat individuals with a number of life-threatening diseases. However, some patients with SCID-X1 developed retroviral vector-mediated leukemia after treatment. The selective growth advantage of gene-modified cells in patients with SCID-X1 suggests that the transgene may have played a role in leukemogenesis. Here we report that 2 of 2...

We review novel gene transfer strategies proposed to be suitable for the treatment Duchenne Muscular Dystrophy (DMD): use of hybrid adeno-retroviral vectors to stably replace dystrophin ultimately in patients lacking this gene and the potential intravenous application of stem cells and monocytes for targeted gene transfer. We discuss the limitations of current vector technology and demonstrate ...

The SV4O-immortalized mouse macrophage cell line, BAC1 .2F5, is strictly dependent on CSF-1 for its survival and proliferation in culture. Introduction of a retroviral vector containing a 1 .6 kilobase (kb) pair human CSF-1 cDNA into these cells abrogated their growth factor dependence but did not render the cells tumorigenic in nude mice. The infected macrophages contained multiple copies of t...

The method of delivering a therapeutic gene into a patient is still one of the major obstacles towards successful human gene therapy. Here we describe a novel gene delivery approach using TheraCyte immunoisolation devices. Retroviral vector producing cells, derived from the avian retrovirus spleen necrosis virus, SNV, were encapsulated in TheraCyte devices and tested for the release of retrovir...

The rat is an excellent model for gene therapy because there are many rat models for human diseases. We have developed a simple and efficient method to deliver genes to the rat liver using recombinant retroviral vectors. A 70% partial hepatectomy followed by retroviral infusion into the portal vein results in 10-15% hepatocyte transduction in vivo. This is 10 times more efficient than in the mo...

Gene transfer into human hematopoietic stem cells with expression targeted to the maturing myelomonocytic progeny has applications for gene therapy of genetic diseases affecting granulocytes and macrophages. We hypothesized that promoters of myeloid-specific genes that are upregulated with myelomonocytic differentiation would also upregulate expression of an exogenous gene in a retroviral vecto...

Retroviral and lentiviral vectors have proven to be particularly efficient systems to deliver genes of interest into target cells, either in vivo or in cell cultures. ey have been used for some time for gene therapy and the development of gene vaccines. Recently retroviral and lentiviral vectors have been used to generate tolerogenic dendritic cells, key professional antigen presenting cells t...

Retroviral vector producer cells (VPC) have been considered genetically stable. A clonal cell population exhibiting a uniform vector integration pattern is used for sustained vector production. Here, we observed that the vector copy number is increased and varied in a population of established LTKOSN.2 VPC. Among five subclones of LTKOSN.2 VPC, the vector copy number ranged from 1 to approximat...