Spatial and temporal control of transgene expression through ultrasound-mediated induction of the heat shock protein 70B promoter in vivo

Roy C. Smith, Marcelle Machluf, Peter Bromley, Anthony Atala, Kenneth Walsh

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Adenoviral vectors have been constructed that express the transgenes luciferase (Adeno-HSP-Luc) or Fas ligand (Adeno-HSP-FasL) under the control of the heat shock protein 70B (hsp70B) promoter. Cultures infected with Adeno-HSP-Luc transiently expressed high levels of luciferase after heat shock. When cultures infected with Adeno-HSP-FasL were maintained at 37°C, no transgene expression was observed, but when cultures were exposed to heat stress, transgene expression resulted in apoptotic cell death. In vivo, transgene expression was induced by ultrasound-mediated heating of adenovirus-infected tissue. In mice or rats injected with the Adeno-HSP-Luc construct, high levels of localized expression of luciferase activity were observed in regions subjected to ultrasound-mediated irradiation. Adeno-HSP-FasL was administered systemically to mice via the tail vein to evaluate safety. Animals receiving Adeno-HSP-FasL in the absence of ultrasound treatment did not display liver toxicity, whereas animals receiving ultrasound treatment to induce the expression of Fas ligand from the hsp70B promoter had significant increases in serum levels of liver enzymes. These data demonstrate that combining the inducible hsp70B promoter with ultrasound induction allows safe local expression of cytotoxic genes with possible therapeutic utility.

Original languageEnglish
Pages (from-to)697-706
Number of pages10
JournalHuman Gene Therapy
Volume13
Issue number6
DOIs
StatePublished - Apr 16 2002
Externally publishedYes

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Fas Ligand Protein
Heat-Shock Proteins
Transgenes
Luciferases
Hot Temperature
Liver
Adenoviridae
Heating
Tail
Veins
Shock
Cell Death
Safety
Gene Expression
Enzymes
Serum

ASJC Scopus subject areas

  • Genetics

Cite this

Spatial and temporal control of transgene expression through ultrasound-mediated induction of the heat shock protein 70B promoter in vivo. / Smith, Roy C.; Machluf, Marcelle; Bromley, Peter; Atala, Anthony; Walsh, Kenneth.

In: Human Gene Therapy, Vol. 13, No. 6, 16.04.2002, p. 697-706.

Research output: Contribution to journalArticle

Smith, Roy C. ; Machluf, Marcelle ; Bromley, Peter ; Atala, Anthony ; Walsh, Kenneth. / Spatial and temporal control of transgene expression through ultrasound-mediated induction of the heat shock protein 70B promoter in vivo. In: Human Gene Therapy. 2002 ; Vol. 13, No. 6. pp. 697-706.
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