Comparison of Gene Transfer Efficiencies and Gene Expression Levels Achieved with Equine Infectious Anemia Virus- and Human Immunodeficiency Virus Type 1-Derived Lentivirus Vectors

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

“…We recently reported that lower gene expression levels of EIAV vectors compared to HIV-1 vectors was attributed, in part, to the relative instability of EIAV derived mRNA. 19 To overcome the low stability, we investigated a variety of post-transcriptional elements in the context of EIAV vectors. Incorporation of the constitutive transport elements CTE and DR-1 resulted in slightly lower gene expression than the parental EIAV vector, similar to our observation of these vectors in mouse skeletal muscle.…”

“…19 Briefly, the woodchuck hepatitis post-transcriptional element (WPRE), the constitutive transport element (CTE) from the Mason-Pfizer monkey virus, or the direct repeat element 1 (DR) from the Rous Sarcoma virus was ligated EIAV transduction of human hematopoietic cells JP O'Rourke et al into the Cla I site of first-generation PEC EIAV vector directly downstream of the enhanced green fluorescent protein (EGFP). The second-generation EIAV self-inactivating vector E-SIN is described (O'Rourke et al 16 and Olsen et al manuscript in preparation.).…”

“…15 EIAV lentivirus vectors have been investigated in a variety of cell and tissue types including rodent skeletal muscle and central nervous system, fetal mice, and a variety of growing and growth arrested cell lines. [16][17][18][19] We recently demonstrated similar gene transfer into human cell lines between EIAV and HIV-1 vectors, suggesting that EIAV vectors may be clinically relevant for human gene transfer. 19 In this report, we demonstrate that EIAV vectors, unlike FIV vectors, transduce a variety of human hematopoietic cell lines and primary human hematopoietic cells.…”

“…[16][17][18][19] We recently demonstrated similar gene transfer into human cell lines between EIAV and HIV-1 vectors, suggesting that EIAV vectors may be clinically relevant for human gene transfer. 19 In this report, we demonstrate that EIAV vectors, unlike FIV vectors, transduce a variety of human hematopoietic cell lines and primary human hematopoietic cells. Furthermore, we begin the optimization of EIAV vectors for use in hematopoietic cells by assessing a variety of posttranscriptional elements and different viral and cellular promoters.…”

Gene- and cell-based therapeutics for type I diabetes mellitus

“…The list indirectly demonstrates that no 'ideal' vector yet exists. New technology, including small interference RNA (siRNA), 31 adeno-associated virus inverted terminal repeat (AAV ITR)-based plasmids, 32,33 novel classes of lentivirus (equine infectious anemia virus-EIAV; feline immunodeficiency virus-FIV), [34][35][36][37][38][39][40] lentivirus-herpesvirus hybrids and other viral vectors is in development, but their efficiency has yet to be reported in the context of Figure 1 Multistep process of insulitis. During ontogeny, a population of thymocytes whose TCR recognize b-cell-specific antigens are either not deleted in the thymus, or fail to be tolerized subsequently, in the periphery.…”