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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ward, C. M. Articles by Seymour, L. W. Search for Related Content PubMed PubMed Citation Articles by Ward, C. M. Articles by Seymour, L. W. Related Collections Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 April 2001, Vol. 97, No. 8, pp. 2221-2229 GENE THERAPY Systemic circulation of poly(L-lysine)/DNA vectors is influenced by polycation molecular weight and type of DNA: differential circulation in mice and rats and the implications for human gene therapy Christopher M. Ward, Martin L. Read, and Leonard W. Seymour From the CRC Institute for Cancer Studies, University of Birmingham, United Kingdom. Effective gene therapy for diseases of the circulation requires vectors capable of systemic delivery. The molecular weight of poly(L-lysine) (pLL) has a significant effect on the circulation of pLL/DNA complexes in mice, with pLL211/DNA complexes displaying up to 20 times greater levels in the blood after 30 minutes compared with pLL20/DNA. It is shown that pLL20/DNA complexes fix mouse complement C3 in vitro, independent of immunoglobulin binding; are less soluble in the blood in vivo; bind erythrocytes; are rapidly removed by the liver, where they associate predominantly with Kupffer cells; and result in a rapid increase in hepatic leukocytes expressing high levels of complement receptor 3 (CR3). The circulation properties of these complexes are also dependent on the type of DNA used, with circular plasmid DNA complexes exhibiting increased circulation compared with linear DNA. PLL211/DNA complexes bind erythrocytes and associate with Kupffer cells but, in contrast, do not fix mouse complement in vitro and are unaffected by the type of DNA used. In rats, both types of complexes produce hematuria and are rapidly removed from the circulation. Correlation of in vivo and in vitro results suggests that the solubility of complexes in physiological saline and species-matched complement fixation and erythrocyte lysis may correlate with systemic circulation. Analysis using human blood in vitro shows no hemolysis, but both types of complexes fix complement and bind IgG, suggesting that pLL/DNA complexes may be rapidly cleared from the human circulation. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. A. Trouw, S. C. Nilsson, I. Goncalves, G. Landberg, and A. M. Blom C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and inhibiting complement activation J. Exp. Med., June 20, 2005; 201(12): 1937 - 1948. [Abstract] [Full Text] [PDF] M. L. Read, S. Singh, Z. Ahmed, M. Stevenson, S. S. Briggs, D. Oupicky, L. B. Barrett, R. Spice, M. Kendall, M. Berry, et al. A versatile reducible polycation-based system for efficient delivery of a broad range of nucleic acids Nucleic Acids Res., May 24, 2005; 33(9): e86 - e86. [Abstract] [Full Text] [PDF] C. Rudolph, C. Plank, J. Lausier, U. Schillinger, R. H. Muller, and J. Rosenecker Oligomers of the Arginine-rich Motif of the HIV-1 TAT Protein Are Capable of Transferring Plasmid DNA into Cells J. Biol. Chem., March 21, 2003; 278(13): 11411 - 11418. [Abstract] [Full Text] [PDF]

	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020