Biosynthesis and characterization of a novel genetically engineered polymer for targeted gene transfer to cancer cells

Brenda F. Canine, Yuhua Wang, Arash Hatefi

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

A novel multi-domain biopolymer was designed and genetically engineered with the purpose to target and transfect cancer cells. The biopolymer contains at precise locations: 1) repeating units of arginine and histidine to condense pDNA and lyse endosome membranes, 2) a HER2 targeting affibody to target cancer cells, 3) a pH responsive fusogenic peptide to destabilize endosome membranes and enhance endosomolytic activity of histidine residues, and 4) a nuclear localization signal to enhance translocation of pDNA towards the cell nucleus. The results demonstrated that the biopolymer was able to condense pDNA into nanosize particles, protect pDNA from serum endonucleases, target HER2 positive cancer cells but not HER2 negative ones, efficiently disrupt endosomes, and effectively reach the cell nucleus of target cells to mediate gene expression. To reduce potential toxicity and enhance biodegradability, the biopolymer was designed to be susceptible to digestion by endogenous furin enzymes inside the cells. The results revealed no significant biopolymer related toxicity as determined by impact on cell viability.

Original languageEnglish (US)
Pages (from-to)188-196
Number of pages9
JournalJournal of Controlled Release
Volume138
Issue number3
DOIs
StatePublished - Sep 15 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • Biomimetic vector
  • Biopolymer
  • Gene therapy
  • Genetically engineered polymer
  • Non-viral vector

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