Abstract | BACKGROUND: Targeted, specific receptor mediated gene transfer is a major goal of gene therapy research to accomplish gene transfer exclusively to the desired cell population. METHODS: First, the use of natural receptor for stem cell factor and transferrin receptor-targeted gene transfer using poly- L-lysine-based molecular conjugate vectors was evaluated in a panel of hematopoietic progenitor cell lines. Second, the ability of poly- L-lysine to enhance adenovirus mediated gene transfer efficiency was examined in different cell lines by using recombinant adenovirus-poly- L-lysine molecular conjugate conglomerates (recMCVEGFP). RESULTS: Despite effective ligand internalization receptor, gene expression amplification in receptor positive cell lines was not uniformly observed. Therefore, using a poly- L-lysine-based, receptor-targeted vector, neither transferrin nor natural receptor for stem cell factor mediated gene transfer can be considered a universally applicable procedure that exclusively depends on the presence of receptors on the cell surface; rather, it is a cell specific phenomenon. In our model, poly- L-lysine is the major contributor for gene transfer to hematopoietic progenitor cells, mediating the initial vector-cell binding. Human progenitor cell lines are poorly transduceable with recombinant adenovirus vectors. This new poly- L-lysine-modified, adenovirus-based vector could overcome virus tropism restrictions and consistently achieve very high transduction efficiency (>90%) in cells otherwise refractory to adenovirus gene transfer. CONCLUSIONS:
Polylysine-based adenovirus vectors may have promise for situations in which high-efficiency gene transfer with transient high level transgene expression in hematopoietic cells is needed, such as leukemia vaccine protocols or for purging strategies in leukemia cell contaminated stem cell preparations.
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Authors | P Schwarzenberger, W Huang, P Oliver, T Osidipe, C Theodossiou, J K Kolls |
Journal | The American journal of the medical sciences
(Am J Med Sci)
Vol. 321
Issue 2
Pg. 129-36
(Feb 2001)
ISSN: 0002-9629 [Print] United States |
PMID | 11217815
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- CLMP protein, human
- Coxsackie and Adenovirus Receptor-Like Membrane Protein
- Receptors, Transferrin
- Receptors, Virus
- Polylysine
- Proto-Oncogene Proteins c-kit
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Topics |
- Adenoviruses, Human
(genetics)
- Carcinoma, Non-Small-Cell Lung
(pathology)
- Cell Adhesion
- Cell Line
- Coxsackie and Adenovirus Receptor-Like Membrane Protein
- Endocytosis
- Eye Neoplasms
(pathology)
- Genes, Reporter
- Genetic Vectors
(administration & dosage, genetics)
- Hematopoietic Stem Cells
(drug effects)
- Humans
- K562 Cells
(drug effects)
- Leukemia, Megakaryoblastic, Acute
(pathology)
- Leukemia, Monocytic, Acute
(pathology)
- Lung Neoplasms
(pathology)
- Neoplastic Stem Cells
(drug effects)
- Polylysine
(administration & dosage, pharmacology)
- Proto-Oncogene Proteins c-kit
(drug effects)
- Receptors, Transferrin
(drug effects)
- Receptors, Virus
(drug effects)
- Retinoblastoma
(pathology)
- Transfection
(methods)
- Tumor Cells, Cultured
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