Transduction potential of human retroviruses in highly proliferating small-cell lung cancer cells as well as non-proliferating hematopoietic stem cells.
Direct gene transfer to solid tissues or metastatic cancer cells requires vectors capable of in vivo transduction to specific cells. The predominant retroviral vectors of murine origin are inactivated by human complement, which precludes their use in vivo. Such inactivation does not take place with vectors based on human retroviruses. Murine retroviral vectors are also limited to proliferating cells, which human retroviruses are not. In this study we examined whether or not a vector using components from the human retroviruses HIV-1 and HTLV-1 could infect small-cell lung cancer cells and resting CD34+ hematopoietic stem cells. While HIV-1 itself was unable to infect cells lacking the CD4-membrane molecule, chimeric viral particles (pseudotype virus) with HIV-1 genome and HTLV-1 envelope components were able to infect both CD4-containing lymphocytic cells, CD4-negative tumour cells and hematopoietic stem cells. After infection with the pseudotype vector, the RNA genome was reverse transcribed and integrated. Transduction efficiency and gene expression under the HIV-1 LTR promoter in both tumour and stem cells were found to be of a similar or greater magnitude than in lymphocytic cells. These results suggest that gene transfer targeting proliferating as well as resting cells in vivo may be realized using components from human retroviruses.
Hansen
J E
JE
Department 144, Hvidovre Hospital, Denmark.
Gram
G J
GJ
Nielsen
S D
SD
Sørensen
A
A
Jensen
P B
PB
Sehested
M
M
Nielsen
J O
JO
Rørth
M
M
D018952:Antigens, CD34 / Q000032:analysis; D018288:Carcinoma, Small Cell / Q000821:virology*; D002455:Cell Division; D004279:DNA, Viral / Q000032:analysis; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D015497:HIV-1 / Q000254:growth & development; D006412:Hematopoietic Stem Cells / Q000821:virology*; D006801:Humans; D011533:Proviruses / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D018952:Antigens, CD34; D004279:DNA, Viral