HIV, but not murine leukemia virus, vectors mediate high efficiency gene transfer into freshly isolated G ₀ /G ₁ human hematopoietic stem cells

Abstract

Recent studies have opened the possibility that quiescent, G 0

Regression of prostate cancer xenografts by a lentiviral vector specifically expressing diphtheria toxin A

“…Generally, highest expression is demonstrated within the first week postinfection and then expression of the gene carried by the infected lentiviral vector decreases. 10,11 Such effects are also demonstrated in our tests. In most cases, tumor regressions were demonstrated within one week.…”

“…Similar strategy has been used by many laboratories. [7][8][9][10][11][12][13] The addition of this protein greatly increases gene transduction. However, since VSV-G is not tissue-specific, lentiviral vectors with this protein on their envelope infect many types of cells.…”

“…[7][8][9][10][11][12][13][14] The crude viral suspension harvested from transfected 293T cell cultures was quantified by measuring levels of the Gag protein, p24, in viral stocks. Infectious titers of the viral vector containing the EGFP reporter were also determined, using limited dilution to infect LNCaP cells.…”

“…No pathogenic effects were observed in the five treated mice for 90 days, suggesting that the PSAR-PCPSA promoter can efficiently control expression of the DTA gene in vivo by limiting toxic gene expression to prostate cells, thereby providing a safe means of treating prostate cancer. As the expression of the gene carried by the infected lentiviral vector decreases to less than 3% at 90 days postinfection in various tissues, 10,11 it is unlikely additional pathogenic effects could be developed after 90 days postinjection. We also collected the organs that are more liable to lentiviral infection, including the spleen, kidney, lung and liver from mice injected with the DTA vector and from mice injected with medium only.…”

“…Lentiviral vectors offer efficacious gene delivery. [7][8][9][10][11] Lentiviral vectors are enclosed by an envelope derived from the host (human) cell membrane. Although there are some considerations concerning the safety of lentiviral vectors, since some sequences are derived from HIV (comprised of B25% HIV sequences), this type of gene therapy vector has been proven to be very safe.…”