Design of imidazole-containing endosomolytic biopolymers for gene delivery

Daniel W. Pack, David Putnam, Robert Langer

Research output: Contribution to journalArticlepeer-review

267 Scopus citations

Abstract

The development of safe and effective gene delivery agents poses a great challenge in the quest to make human gene therapy a reality. Cationic polymers represent one important class of materials for gene delivery, but to date they have shown only moderate efficiency. Improving the efficiency will require the design of new polymers incorporating optimized gene delivery properties. For example, inefficient release of the DNA/polymer complex from endocytic vesicles into the cytoplasm is one of the primary causes of poor gene delivery. Here we report the synthesis of a biocompatible, imidazole- containing polymer designed to overcome this obstacle. DNA/polymer polyplexes incorporating this polymer were shown to have desirable physico-chemical properties for gene delivery and are essentially nontoxic. Using this system, mammalian cells in vitro were transfected in the absence of any exogenous endosomolytic agent such as chloroquine.

Original languageEnglish
Pages (from-to)217-223
Number of pages7
JournalBiotechnology and Bioengineering
Volume67
Issue number2
DOIs
StatePublished - Jan 20 2000

Keywords

  • Chloroquine
  • Endosomolytic polymer
  • Gene delivery
  • Polycations
  • Polyhistidine
  • Polyplexes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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