Efficacy and safety of sleeping beauty transposon-mediated gene transfer in preclinical animal studies

Perry B Hackett, Elena L Aronovich, David Hunter, Myra Urness, Jason B. Bell, Steven J. Kass, Laurence J.N. Cooper, R S Mc Ivor

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Sleeping Beauty (SB) transposons have been effective in delivering therapeutic genes to treat certain diseases in mice. Hydrodynamic gene delivery of integrating transposons to 5-20% of the hepatocytes in a mouse results in persistent elevated expression of the therapeutic polypeptides that can be secreted into the blood for activity throughout the animal. An alternative route of delivery is ex vivo transformation with SB transposons of hematopoietic cells, which then can be reintroduced into the animal for treatment of cancer. We discuss issues associated with the scale-up of hydrodynamic delivery to the liver of larger animals as well as ex vivo delivery. Based on our and others' experience with inefficient delivery to larger animals, we hypothesize that impulse, rather than pressure, is a critical determinant of the effectiveness ofhydrodynamic delivery. Accordingly, we propose some alterations in delivery strategies that may yield efficacious levels of gene delivery in dogs and swine that will be applicable to humans. To ready hydrodynamic delivery for human application we address a second issue facing transposons used for gene delivery regarding their potential to "re-hop" from one site to another and thereby destabilize the genome. The ability to correct genetic diseases through the infusion of DNA plasmids remains an appealing goal.

Original languageEnglish (US)
Pages (from-to)341-349
Number of pages9
JournalCurrent gene therapy
Volume11
Issue number5
StatePublished - Oct 1 2011

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Beauty
Hydrodynamics
Safety
Genes
Humulus
Inborn Genetic Diseases
Aptitude
Hepatocytes
Plasmids
Swine
Genome
Dogs
Pressure
Peptides
Liver
DNA
Therapeutics
Neoplasms

Keywords

  • Chimeric antigen receptors
  • Clinical applications
  • Hydrodynamic gene delivery
  • Non-viral gene delivery
  • Sleeping beauty transposons
  • T-cells

Cite this

Efficacy and safety of sleeping beauty transposon-mediated gene transfer in preclinical animal studies. / Hackett, Perry B; Aronovich, Elena L; Hunter, David; Urness, Myra; Bell, Jason B.; Kass, Steven J.; Cooper, Laurence J.N.; Mc Ivor, R S.

In: Current gene therapy, Vol. 11, No. 5, 01.10.2011, p. 341-349.

Research output: Contribution to journalArticle

Hackett, Perry B ; Aronovich, Elena L ; Hunter, David ; Urness, Myra ; Bell, Jason B. ; Kass, Steven J. ; Cooper, Laurence J.N. ; Mc Ivor, R S. / Efficacy and safety of sleeping beauty transposon-mediated gene transfer in preclinical animal studies. In: Current gene therapy. 2011 ; Vol. 11, No. 5. pp. 341-349.
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