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A pH-Sensitive Polymer That Enhances Cationic Lipid-Mediated Gene Transfer

Cheung, Charles Y., Murthy, Niren, Stayton, Patrick S., Hoffman, Allan S.·2001·Bioconjugate Chemistry

Abstract

The efficient release of nonviral gene carriers from endosomes is an important step for the successful delivery of DNA into the cell nucleus. A synthetic pH-sensitive anionic polymer, poly(propylacrylic acid) (PPAA), was designed to aid in endosomal escape of nonviral vectors and improve the transfection efficiencies with these vectors. Transfection of NIH3T3 fibroblasts with ternary physical mixtures of the cationic lipid DOTAP, pCMVbeta plasmid DNA, and PPAA showed marked enhancement of both gene expression levels and fraction of cells transfected compared to binary control mixtures of DOTAP and DNA. PPAA also significantly improved the serum-stability of DOTAP/DNA vectors. The DOTAP/DNA/PPAA vectors maintained high levels of transfection in media containing up to 50% serum. The striking enhancement of transfection efficiency with cationic lipid/DNA/PPAA mixtures, along with the enhanced serum-stability, suggests that PPAA may provide significant improvements for the in vivo intracellular delivery of drugs such as DNA, oligonucleotides, proteins, and peptides.

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Authors
Cheung, C. Y., Murthy, N., Stayton, P. S., & Hoffman, A. S.
Venue
Bioconjugate Chemistry
Published
2001-10-27
Volume
12
Issue
6
Pages
906-910
ISSN
  • 1043-1802 (ISSN-L)
  • 1520-4812
OpenAlex
W2021741932
Cited by
164
References
0
FWCI
2.50
Type
journal article
Language
en
Open access
closed

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