Innovative approaches to the use of polyamines for DNA nanoparticle preparation for gene therapy

Veena Vijayanathan, Enzo Agostinelli, Thresia Thomas, T. J. Thomas

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Advances in genomic technologies, such as next generation sequencing and disease specific gene targeting through anti-sense, anti-gene, siRNA and microRNA approaches require the transport of nucleic acid drugs through the cell membrane. Membrane transport of DNA/RNA drugs is an inefficient process, and the mechanism(s) by which this process occurs is not clear. A pre-requisite for effective transport of DNA and RNA in cells is their condensation to nanoparticles of ∼100 nm size. Although viral vectors are effective in gene therapy, the immune response elicited by viral proteins poses a major challenge. Multivalent cations, such as natural polyamines are excellent promoters of DNA/RNA condensation to nanoparticles. During the past 20 years, our laboratory has synthesized and tested several analogs of the natural polyamine, spermine, for their efficacy to provoke DNA condensation to nanoparticles. We determined the thermodynamics of polyamine-mediated DNA condensation, measured the structural specificity effects of polyamine analogs in facilitating the cellular uptake of oligonucleotides, and evaluated the gene silencing activity of DNA nanoparticles in breast cancer cells. Polyamine-complexed oligonucleotides showed a synergistic effect on target gene inhibition at the mRNA level compared to the use of polyamines and oligonucleotides as single agents. Ionic and structural specificity effects were evident in DNA condensation and cellular transportation effects of polyamines. In condensed DNA structures, correlation exists between the attractive and repulsive forces with structurally different polyamines and cobalt hexamine, indicating the existence of a common force in stabilizing the condensed structures. Future studies aimed at defining the mechanism(s) of DNA compaction and structural features of DNA nanoparticles might aid in the development of novel gene delivery vehicles.

Original languageEnglish (US)
Pages (from-to)499-509
Number of pages11
JournalAmino Acids
Volume46
Issue number3
DOIs
StatePublished - 2014

Fingerprint

Gene therapy
Polyamines
Genetic Therapy
Nanoparticles
DNA
Condensation
Genes
RNA Transport
Oligonucleotides
RNA
Methenamine
Spermine
Gene Targeting
Gene Silencing
Viral Proteins
Cell membranes
Cobalt
MicroRNAs
Thermodynamics
Pharmaceutical Preparations

Keywords

  • DNA condensation
  • Gene delivery
  • Gene therapy
  • Nanoparticles
  • Polyamines
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry
  • Medicine(all)

Cite this

Innovative approaches to the use of polyamines for DNA nanoparticle preparation for gene therapy. / Vijayanathan, Veena; Agostinelli, Enzo; Thomas, Thresia; Thomas, T. J.

In: Amino Acids, Vol. 46, No. 3, 2014, p. 499-509.

Research output: Contribution to journalArticle

Vijayanathan, Veena ; Agostinelli, Enzo ; Thomas, Thresia ; Thomas, T. J. / Innovative approaches to the use of polyamines for DNA nanoparticle preparation for gene therapy. In: Amino Acids. 2014 ; Vol. 46, No. 3. pp. 499-509.
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