Therapeutic success and efficacy of nonviral liposomal cDNA gene transfer to the skin in vivo is dose dependent

M. G. Jeschke, G. Richter, David Herndon, E. K. Geissler, M. Hartl, F. Hofstätter

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

It is well documented that responses to growth factor treatment typically display bell-shaped dose responses that can significantly affect efficacy. Here we tested the hypothesis that nonviral liposomal gene delivery also displays this characteristic. We chose two different growth factors, keratinocyte growth factor (KGF) and insulin-like growth factor-I (IGF-I) CMV-driven transfecting constructs at three different concentrations and assessed efficacy on several physiological parameters that are descriptive of wound healing progress in a burn-wound healing model. Rats were given a 60% TBSA scald burn and randomly divided into one of seven groups to receive weekly subcutaneous injections of liposomes containing the cDNA for KGF (0.2 μg, 2.2 μg, or 22.2 μg), or liposomes containing the cDNA for IGF-I (0.2 μg, 2.2 μg, or 22.2 μg) at various concentrations, but constant liposome:DNA ratios and a LacZ gene (0.2 μg) CMV-driven construct for β-galactosidase as vehicle and marker gene. Transfection was confirmed by histology for β-galactosidase. Physiological efficacy was evaluated by measuring the wound healing parameters that define dermal and epidermal regeneration. Transfection products were found in the cytoplasm of rapidly dividing cells of the granulation tissue. Different doses of the non viral cDNA gene transfer coding for KGF or IGF-I resulted in different outcomes for dermal and epidermal regeneration. There was a dose-dependent response to both growth factor gene transfers that was not dissimilar from that typically displayed by treatment with growth factor proteins. Both concentrations below and above the optimal concentration of DNA:liposomal preparations did not yield the results observed at the optimal concentration.

Original languageEnglish (US)
Pages (from-to)1777-1784
Number of pages8
JournalGene Therapy
Volume8
Issue number23
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Fibroblast Growth Factor 7
Intercellular Signaling Peptides and Proteins
Complementary DNA
Insulin-Like Growth Factor I
Galactosidases
Liposomes
Wound Healing
Skin
Genes
Transfection
Regeneration
Lac Operon
Viral Genes
Granulation Tissue
DNA
Subcutaneous Injections
Therapeutics
Burns
Histology
Cytoplasm

Keywords

  • Gene therapy
  • Growth factors
  • KGF
  • Skin
  • Thermal injury
  • Wound healing

ASJC Scopus subject areas

  • Genetics

Cite this

Jeschke, M. G., Richter, G., Herndon, D., Geissler, E. K., Hartl, M., & Hofstätter, F. (2001). Therapeutic success and efficacy of nonviral liposomal cDNA gene transfer to the skin in vivo is dose dependent. Gene Therapy, 8(23), 1777-1784. https://doi.org/10.1038/sj.gt.3301589

Therapeutic success and efficacy of nonviral liposomal cDNA gene transfer to the skin in vivo is dose dependent. / Jeschke, M. G.; Richter, G.; Herndon, David; Geissler, E. K.; Hartl, M.; Hofstätter, F.

In: Gene Therapy, Vol. 8, No. 23, 2001, p. 1777-1784.

Research output: Contribution to journalArticle

Jeschke, MG, Richter, G, Herndon, D, Geissler, EK, Hartl, M & Hofstätter, F 2001, 'Therapeutic success and efficacy of nonviral liposomal cDNA gene transfer to the skin in vivo is dose dependent', Gene Therapy, vol. 8, no. 23, pp. 1777-1784. https://doi.org/10.1038/sj.gt.3301589
Jeschke, M. G. ; Richter, G. ; Herndon, David ; Geissler, E. K. ; Hartl, M. ; Hofstätter, F. / Therapeutic success and efficacy of nonviral liposomal cDNA gene transfer to the skin in vivo is dose dependent. In: Gene Therapy. 2001 ; Vol. 8, No. 23. pp. 1777-1784.
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