Characterization of vectors for gene therapy formed by self-assembly of DNA with synthetic block co-polymers

Margreet A. Wolfert, Etienne H. Schacht, Veska Toncheva, Karel Ulbrich, Ola Nazarova, Leonard W. Seymour

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Cationic polymers can self-assemble with DNA to form polyelectrolyte complexes capable of gene delivery, although biocompatibility of the complexes is generally limited. Here we have used A-B type cationic-hydrophilic block co-polymers to introduce a protective surface hydrophilic shielding following oriented self-assembly with DNA. Block co-polymers of poly(ethylene glycol)-poly-L-lysine (pEG-pLL) and poly-N-(2-hydroxypropyl)methacrylamide-poly(trimethylammonioethyl methacrylate chloride) (pHPMA-pTMAEM) both show spontaneous formation of complexes with DNA. Surface charge measured by zeta potential is decreased compared with equivalent polycation-DNA complexes in each case. Atomic force microscopy shows that pHPMA-pTMAEM/DNA complexes are discrete spheres similar to those formed between DNA and simple polycations, whereas pEG-pLL/DNA complexes adopt an extended structure. Biological properties depend on the charge ratio of formation. At optimal charge ratio, pEG-pLL/DNA complexes show efficient transfection of 293 cells in vitro, while pHPMA-pTMAEM/DNA complexes are more inert. Both block co-polymer-DNA complexes show only limited cytotoxicity. Careful selection of block co-polymer structure can influence the physicochemical and biological properties of the complexes and should permit design of materials for specific applications, including targeted delivery of genes in vivo.
Original languageEnglish
Pages (from-to)2123-2133
Number of pages11
JournalHuman Gene Therapy
Volume7
Issue number17
Publication statusPublished - 10 Nov 1996
Externally publishedYes

Keywords

  • biomaterial
  • copolymer
  • macrogol
  • polyelectrolyte
  • polylysine
  • polymethacrylic acid derivative
  • article
  • atomic force microscopy
  • biocompatibility
  • controlled study
  • cytotoxicity
  • DNA synthesis
  • expression vector
  • fetus
  • gene targeting
  • gene therapy
  • genetic transfection
  • human
  • human cell
  • hydrophilicity
  • physical chemistry

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