| RRC ID |
21519
|
| Author |
Kaneko E, Kawahara M, Ueda H, Nagamune T.
|
| Title |
Growth control of genetically modified cells using an antibody/c-Kit chimera.
|
| Journal |
J Biosci Bioeng
|
| Abstract |
Gene therapy has been regarded as an innovative potential treatment against serious congenital diseases. However, applications of gene therapy remain limited, partly because its clinical success depends on therapeutic gene-transduced cells acquiring a proliferative advantage. To address this problem, we have developed the antigen-mediated genetically modified cell amplification (AMEGA) system, which uses chimeric receptors to enable the selective proliferation of gene-transduced cells. In this report, we describe mimicry of c-Kit signaling and its application to the AMEGA system. We created an antibody/c-Kit chimera in which the extracellular domain of c-Kit is replaced with an anti-fluorescein single-chain Fv antibody fragment and the extracellular D2 domain of the erythropoietin receptor. A genetically modified mouse pro-B cell line carrying this chimera showed selective expansion in the presence of fluorescein-conjugated BSA (BSA-FL) as a growth inducer. By further engineering the transmembrane domain of the chimera to reduce interchain interaction we attained stricter ligand-dependency. Since c-Kit is an important molecule in the expansion of hematopoietic stem cells (HSCs), this antibody/c-Kit chimera could be a promising tool for gene therapy targeting HSCs.
|
| Volume |
113(5)
|
| Pages |
641-6
|
| Published |
2012-5-1
|
| DOI |
10.1016/j.jbiosc.2011.12.005
|
| PII |
S1389-1723(11)00520-2
|
| PMID |
22227120
|
| MeSH |
Animals
Antibodies / metabolism*
Antigens / metabolism
Cell Line
Cell Proliferation
Chimera / metabolism*
Genetic Therapy
Hematopoietic Stem Cells / cytology*
Humans
Mice
Precursor Cells, B-Lymphoid
Receptors, Erythropoietin / genetics
Receptors, Erythropoietin / metabolism
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / immunology
Recombinant Fusion Proteins / metabolism
Signal Transduction
Single-Chain Antibodies / genetics
|
| IF |
2.366
|
| Times Cited |
17
|
|
WOS Category
|
FOOD SCIENCE & TECHNOLOGY
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
|
| Resource |
| DNA material |
pUC kit EH1 (RDB01344) |
