Genetic manipulation of primitive leukemic and normal hematopoietic cells using a novel method of adenovirus-mediated gene transfer

D. S. Howard, D. A. Rizzierri, B. Grimes, D. Upchurch, G. L. Phillips, A. K. Stewart, J. R. Yannelli, C. T. Jordan

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Gene transfer into early hematopoietic cells has been problematic due to the quiescent nature of primitive cells and the lack of gene transfer vehicles with high efficiency for hematopoietic cell types. Previously, we have shown that adenoviral vectors can be used for the transduction of normal human progenitors with gene transfer efficiencies of approximately 30%. However, this approach is limited by relatively slow uptake kinetics (24-48 h) and a strong dependence on the presence of exogenous cytokines. Thus, we have modified this approach by combining adenoviral vectors with polycations to generate a virus-polycation complex, or VPC. Vehicles of this nature, when composed of conventional adenoviral vectors and polyamidoamine dendrimers, are a highly efficient means of transducing both normal and acute myelogenous leukemia (AML) cells. Moreover, the kinetics of gene transfer are markedly increased using the VPC strategy, with approximately 70% of transduction complete within 2 h. In this study, using viruses that encode green fluorescence protein (GFP), or the T cell costimulatory molecule B7.1 (CD80), we show that VPC-mediated gene transfer is an effective means of transducing normal and AML cells, including those with a highly primitive phenotype. Our data suggest that transient genetic manipulation of primitive hematopoietic cells can readily be achieved and should therefore permit a variety of research and clinical endeavors.

Original languageEnglish
Pages (from-to)1608-1616
Number of pages9
Issue number10
StatePublished - 1999

Bibliographical note

Funding Information:
This work was supported by grants from the McDowell Cancer Foundation and the Leukemia Society of America (Translational Grant #6057-99). The authors thank the McDowell Cancer Foundation for generous support of our research efforts. We also thank Dr Stephen Szilvassy for critical reading of the manuscript and many helpful discussions, and Dr Stephen Hardy for providing the Ad-GFP virus and protocols for the use of adenoviral vectors. The Ad-B7 virus was generously provided by Dr Sophie Dessureault.


  • Acute myelogenous leukemia (AML)
  • Adenovirus
  • CD80
  • Gene transfer
  • Hematopoietic
  • Leukemia

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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