Optimization of ultrasound-mediated gene transfer: Comparison of contrast agents and ultrasound modalities

Sorin V. Pislaru, Cristina Pislaru, Randall R. Kinnick, Ripudamanjit Singh, Rajiv Gulati, James F. Greenleaf, Robert D. Simari

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

Aims: Ultrasound (US)-enhanced gene transfer for cardiovascular disease is an emerging technique with translational relevance. Prior to pre-clinical applications, optimization of gene transfer using various US contrast agents and parameters is required. In order to do so, two clinically relevant contrast agents (Optison and PESDA), and two US modalities (dedicated continuous wave system and diagnostic scanner) were tested in vitro and in vivo. Methods and Results: In vitro, luciferase activity was measured after exposure of primary vascular cells to combinations of luciferase plasmid, contrast agents, and US exposures. US gene transfer was consistently superior to controls. PESDA was better than Optison; there was no significant difference between US modalities. In vivo, luciferase activity in skeletal muscle of rats was measured after injection of plasmid or adenovirus, expressing luciferase with or without US exposure. Diagnostic US was superior to continuous wave. US plasmid gene transfer was highly localized, and was superior to all controls except adenovirus which lacked spatial specificity. To deliver a secreted transgene product, US gene transfer of a plasmid expressing tissue factor pathway inhibitor (TFPI) to skeletal muscle resulted in a dose-related increase in plasma activity for up to 5 days after delivery. Conclusion: US-enhanced plasmid gene transfer is capable of transducing skeletal muscle in vivo either directly or via an intravascular route. This enhanced nonviral method is an alternative to plasmid DNA alone or viral vectors.

Original languageEnglish (US)
Pages (from-to)1690-1698
Number of pages9
JournalEuropean heart journal
Volume24
Issue number18
DOIs
StatePublished - Sep 1 2003

Keywords

  • Contrast agents
  • Gene transfer
  • Ultrasound

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Optimization of ultrasound-mediated gene transfer: Comparison of contrast agents and ultrasound modalities'. Together they form a unique fingerprint.

  • Cite this