Substrate-mediated DNA delivery: role of the cationic polymer structure and extent of modification.

Published

Journal Article

DNA complex immobilization to substrates that support cell adhesion can enhance gene transfer by maintaining DNA within the cellular environment while limiting complex aggregation. This report examines the tether design (e.g., extent of functionalization) and cationic polymer structure for their effect on complex binding to the substrate and cellular transfection. DNA is complexed with cationic polymers (polylysine, PL; polyethylenimine, PEI), which are functionalized with biotin for binding to a neutravidin (NA) substrate. Surfaces densities ranging from 0.4 to 2.6 microg DNA/cm(2) were obtained for PL, and from 0.7 to 1.0 microg DNA/cm(2) for PEI. The distribution of biotin groups for PL/DNA complexes had a dual effect on cellular transfection. Increasing the fraction of PL with biotin residues decreased luciferase activity; however, increasing the number of biotin residues per PL increased luciferase activity. For PEI, the number of biotin groups present on the complex did not affect transgene expression. Release studies demonstrated that 20-30% of the immobilized DNA was released over 8 days, with 8-20% released during the first 24 h. Enzymatic degradation of cationic polymers is not necessary for transfection. Additionally, the duration of transgene expression was extended for surface-mediated delivery relative to bolus delivery.

Full Text

Duke Authors

Cited Authors

  • Segura, T; Volk, MJ; Shea, LD

Published Date

  • November 2003

Published In

Volume / Issue

  • 93 / 1

Start / End Page

  • 69 - 84

PubMed ID

  • 14602423

Pubmed Central ID

  • 14602423

Electronic International Standard Serial Number (EISSN)

  • 1873-4995

International Standard Serial Number (ISSN)

  • 0168-3659

Digital Object Identifier (DOI)

  • 10.1016/j.jconrel.2003.08.003

Language

  • eng