Rationally designed Escherichia coli cytosine deaminase mutants with improved specificity towards the prodrug 5-fluorocytosine for potential gene therapy applications

MedChemComm ◽  
2012 ◽  
Vol 3 (10) ◽  
pp. 1316 ◽  
Author(s):  
V. Kohila ◽  
Amit Jaiswal ◽  
Siddhartha Sankar Ghosh
Keyword(s):  
Escherichia Coli ◽  
Gene Therapy ◽  
Cytosine Deaminase

scholarly journals Random mutagenesis and selection of Escherichia coli cytosine deaminase for cancer gene therapy

2004 ◽  
Vol 17 (8) ◽  
pp. 625-633 ◽  
Author(s):  
S. D. Mahan ◽  
G. C. Ireton ◽  
C. Knoeber ◽  
B. L. Stoddard ◽  
M. E. Black
Keyword(s):  
Escherichia Coli ◽  
Gene Therapy ◽  
Cytosine Deaminase ◽  
Random Mutagenesis ◽  
Cancer Gene Therapy ◽  
Cancer Gene ◽  
Selection Of

scholarly journals Mutation of Escherichia coli cytosine deaminase significantly enhances molecular chemotherapy of human glioma

Gene Therapy ◽  
2007 ◽  
Vol 14 (14) ◽  
pp. 1111-1119 ◽  
Author(s):  
S A Kaliberov ◽  
J M Market ◽  
G Y Gillespie ◽  
V Krendelchtchikova ◽  
D Della Manna ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cytosine Deaminase ◽  
Human Glioma ◽  
Molecular Chemotherapy

Location of the gene specifying cytosine deaminase in Escherichia coli

1972 ◽  
Vol 118 (4) ◽  
pp. 323-325 ◽  
Author(s):  
S. I. Ahmad ◽  
R. H. Pritchard
Keyword(s):  
Escherichia Coli ◽  
Cytosine Deaminase

scholarly journals Imaging Expression of Cytosine Deaminase-Herpes Virus Thymidine Kinase Fusion Gene (CD/TK) Expression with [124I]FIAU and PET

2002 ◽  
Vol 1 (1) ◽  
pp. 153535002002000 ◽  
Author(s):  
Trevor Hackman ◽  
Michail Doubrovin ◽  
Julius Balatoni ◽  
Tatiana Beresten ◽  
Vladimir Ponomarev ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Thymidine Kinase ◽  
Enzyme Assay ◽  
Fusion Gene ◽  
Cytosine Deaminase ◽  
Prodrug Activation ◽  
Wide Range ◽  
Different Levels

Double prodrug activation gene therapy using the Escherichia coli cytosine deaminase (CD)herpes simplex virus type 1 thymidine kinase ( HSV1-tk) fusion gene ( CD/TK) with 5-fluorocytosine (5FC), ganciclovir (GCV), and radiotherapy is currently under evaluation for treatment of different tumors. We assessed the efficacy of noninvasive imaging with [124I]FIAU (2′-fluoro-2′-deoxy-1-β-d-arabinofuranosyl-5-iodo-uracil) and positron emission tomography (PET) for monitoring expression of the CD/TK fusion gene. Walker-256 tumor cells were transduced with a retroviral vector bearing the CD/TK gene (W256CD/TK cells). The activity of HSV1-TK and CD subunits of the CD/TK gene product was assessed in different single cell-derived clones of W256CD/TK cells using the FIAU radiotracer accumulation assay in cells and a CD enzyme assay in cell homogenates, respectively. A linear relationship was observed between the levels of CD and HSV1-tk subunit expression in corresponding clones in vitro over a wide range of CD/TK expression levels. Several clones of W256CD/TK cells with significantly different levels of CD/TK expression were selected and used to produce multiple subcutaneous tumors in rats. PET imaging of HSV1-TK subunit activity with [124I]FIAU was performed on these animals and demonstrated that different levels of CD/TK expression in subcutaneous W256CD/TK tumors can be imaged quantitatively. CD expression in subcutaneous tumor sample homogenates was measured using a CD enzyme assay. A comparison of CD and HSV1-TK subunit enzymatic activity of the CD/TK fusion protein in vivo showed a significant correlation. Knowing this relationship, the parametric images of CD subunit activity were generated. Imaging with [124I]FIAU and PET could provide pre- and posttreatment assessments of CD/TK-based double prodrug activation in clinical gene therapy trials.

Liposomal formulation of 5-fluorocytosine in suicide gene therapy with cytosine deaminase – for colorectal cancer

2008 ◽  
Vol 262 (2) ◽  
pp. 164-172 ◽  
Author(s):  
Monika Chaszczewska-Markowska ◽  
Katarzyna Stebelska ◽  
Aleksander Sikorski ◽  
Janusz Madej ◽  
Adam Opolski ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Therapy ◽  
Cytosine Deaminase ◽  
Suicide Gene ◽  
Suicide Gene Therapy ◽  
Liposomal Formulation
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