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Nucleic Acids Research 2005 33(4):e40; doi:10.1093/nar/gni040
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Published online 24 February 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
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Methods Online

Modified branched peptides with a histidine-rich tail enhance in vitro gene transfection

Qixin Leng and A. James Mixson*

Department of Pathology, University of Maryland Baltimore MSTF Building, 10 South Pine Street, Baltimore, MD 21201, USA

*To whom correspondence should be addressed. Tel: +1 410 706 3223; Fax: +1 410 706 8414; Email: amixson{at}umaryland.edu

Received October 7, 2004. Accepted February 4, 2005.

Successful gene therapy depends on the development of efficient, non-toxic gene delivery systems. To accomplish this objective, our laboratory has focused on solid-phase synthesized peptide carriers, in which the amino acid sequence can be varied precisely to augment intracellular DNA transport. We previously determined that linear and branched co-polymers of histidine and lysine in combination with liposomes enhanced the efficiency of gene transfection. In this study, we have modified two branched histidine-lysine (HK) peptides by adding a histidine-rich tail. In a variety of cell lines, this histidine-rich tail markedly improved transfection efficiency, presumably by increasing the buffering capacity of the polymer. One polymer with a histidine-rich tail, H2K4bT, compared favorably with the commonly used transfection agents. Together with modification of our transfection protocol, these improved HK peptides alone, without liposomes, are the effective carriers of plasmids into a variety of cells. We anticipate that branched HK peptides will continue to be developed as carriers of nucleic acids for in vitro and in vivo applications.


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