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Palmitic acid substitution on cationic polymers for effective delivery of plasmid DNA to bone marrow stromal cells

✍ Scribed by Vanessa Incani; Emily Tunis; Basak Acan Clements; Cori Olson; Cezary Kucharski; Afsaneh Lavasanifar; Hasan Uludag


Publisher
John Wiley and Sons
Year
2007
Tongue
English
Weight
518 KB
Volume
81A
Category
Article
ISSN
1549-3296

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✦ Synopsis


Abstract

Nonviral gene carriers are actively explored in gene therapy due to safety concerns of the viral carriers. To design effective gene carriers for modification of bone marrow stromal cells (BMSC), an important cell phenotype for clinical application of gene therapy, cationic polymers polyethyleneimine (PEI), and poly‐L‐Lysine (PLL) were substituted with palmitic acid (PA) via amide linkages. Depending on the reaction conditions, PEI and PLL was substituted with 2.2–5.2 and 13.4–16.2 PA per polymer chain. The PA substituted polymers displayed slightly lower binding efficiency towards a plasmid containing Enhanced Green Fluorescent Protein (pEGFP) in an agarose gel binding assay. The cell binding of PLL‐PA, but not PEI‐PA, was particularly enhanced, resulting in higher percentage of the cells displaying a significant polymer uptake. pEGFP delivery into the BMSC was also significantly increased with the PLL‐PA (vs. PLL), but not PEI‐PA (vs. PEI). The transfection efficiency of PLL‐PA was significantly higher (∼fivefold) than the unmodified polymer. We conclude that PA substitution on PLL provides an effective carrier for transfection of primary cells derived from the bone marrow. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007.