Novel vectors for gene delivery formed by self-assembly of DNA with poly(L-lysine) grafted with hydrophilic polymers

Veska Toncheva, Margreet A. Wolfert, Philip R. Dash, David Oupicky, Karel Ulbrich, Leonard W. Seymour, Etienne H. Schacht

Research output: Contribution to journalArticle

250 Citations (Scopus)

Abstract

Complexes formed between DNA and cationic polymers are attracting increasing attention as novel synthetic vectors for delivery of genes. We are trying to improve biological properties of such complexes by oriented self- assembly of DNA with cationic-hydrophilic block copolymers, designed to enshroud the complex within a protective hydrophilic polymer corona. Poly(L- lysine) (pLL) grafted with range of hydrophilic polymer blocks, including poly(ethylene glycol) (pEG), dextran and poly[N-(2- hydroxypropyl)methacrylamide] (pHPMA), shows efficient binding to DNA and mediates particle self-assembly and inhibition of ethidium bromide/DNA fluorescence. The complexes formed are discrete and typically about 100 nm diameter, viewed by atomic force microscopy. Surface charges are slightly shielded by the presence of the hydrophilic polymer, and complexes generally show decreased cytotoxicity compared with simple pLL/DNA complexes. pEG- containing complexes show increased transfection activity against cells in vitro. Complexes formed with all polymer conjugates showed greater aqueous solubility than simple pLL/DNA complexes, particularly at charge neutrality. These materials appear to have the ability to regulate the physicochemical and biological properties of polycation/DNA complexes, and should find important applications in packaging of nucleic acids for specific biological applications.

Original languageEnglish (US)
Pages (from-to)354-368
Number of pages15
JournalBiochimica et Biophysica Acta - General Subjects
Volume1380
Issue number3
DOIs
StatePublished - May 8 1998

Fingerprint

Self assembly
Lysine
Polymers
Genes
DNA
Block copolymers
Ethidium
Ethylene Glycol
Atomic Force Microscopy
Product Packaging
Cytotoxicity
Surface charge
Dextrans
Solubility
Nucleic Acids
Polyethylene glycols
Transfection
Atomic force microscopy
Packaging
Fluorescence

Keywords

  • Block copolymers
  • Gene delivery
  • Gene therapy
  • Self assembly

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Novel vectors for gene delivery formed by self-assembly of DNA with poly(L-lysine) grafted with hydrophilic polymers. / Toncheva, Veska; Wolfert, Margreet A.; Dash, Philip R.; Oupicky, David; Ulbrich, Karel; Seymour, Leonard W.; Schacht, Etienne H.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1380, No. 3, 08.05.1998, p. 354-368.

Research output: Contribution to journalArticle

Toncheva, Veska ; Wolfert, Margreet A. ; Dash, Philip R. ; Oupicky, David ; Ulbrich, Karel ; Seymour, Leonard W. ; Schacht, Etienne H. / Novel vectors for gene delivery formed by self-assembly of DNA with poly(L-lysine) grafted with hydrophilic polymers. In: Biochimica et Biophysica Acta - General Subjects. 1998 ; Vol. 1380, No. 3. pp. 354-368.
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