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Poly-L-lysine-based molecular conjugate vectors: a high efficiency gene transfer system for human progenitor and leukemia cells.

AbstractBACKGROUND:
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.
AuthorsP Schwarzenberger, W Huang, P Oliver, T Osidipe, C Theodossiou, J K Kolls
JournalThe 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
PMID11217815 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • CLMP protein, human
  • Coxsackie and Adenovirus Receptor-Like Membrane Protein
  • Receptors, Transferrin
  • Receptors, Virus
  • Polylysine
  • Proto-Oncogene Proteins c-kit
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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