In vivo gene transfer of a suicide gene under the transcriptional control of the carcinoembryonic antigen promoter results in bone marrow transduction but can avoid bone marrow suppression.
We constructed the CEA419/CD retrovirus vector carrying the cytosine deaminase (CD) gene directed by the carcinoembryonic antigen (CEA) promoter. pCD2 retrovirus vector carrying the CD gene directed by the retrovirus long terminal repeat promoter was also used. When mice bearing intraperitoneally disseminated colorectal carcinomas (CRCs) were infused intraperitoneally with pCD2 or CEA419/CD retrovirus-producing cells, a CD fragment was detected in CRCs and bone marrow cells. It was shown that the CD gene was expressed both in CRCs and in the bone marrow of animals infused with pCD2 retrovirus-producing cells, while the CD gene was expressed solely in CRCs of animals infused with CEA419/CD retrovirus-producing cells. These results indicate that the use of a tumor-selective promoter may warrant the safety of in vivo gene therapy using suicide genes.
Cao
G
G
Department of Microbiology, Second Military Medical University, Shanghai 200433, P.R. China.
Kuriyama
S
S
Gao
J
J
Mitoro
A
A
Cui
L
L
Nagao
S
S
Zhang
X
X
Tsujinoue
H
H
Pan
X
X
Fukui
H
H
Qi
Z
Z
D000230:Adenocarcinoma / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D000818:Animals; D001854:Bone Marrow Cells / Q000821:virology*; D001855:Bone Marrow Diseases / Q000209:etiology / Q000517:prevention & control*; D002272:Carcinoembryonic Antigen / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy*; D043525:Cytosine Deaminase; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000009:adverse effects; D005822:Genetic Vectors / Q000009:adverse effects / Q000235:genetics / Q000302:isolation & purification*; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics; D008980:Moloney murine sarcoma virus / Q000235:genetics; D009368:Neoplasm Transplantation; D009700:Nucleoside Deaminases / Q000235:genetics*; D010534:Peritoneal Neoplasms / Q000556:secondary / Q000628:therapy; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012190:Retroviridae / Q000235:genetics / Q000302:isolation & purification*; D013539:Simian virus 40 / Q000235:genetics; D020079:Terminal Repeat Sequences / Q000235:genetics*; D014158:Transcription, Genetic
D002272:Carcinoembryonic Antigen; D011993:Recombinant Fusion Proteins; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase