Targeted tissue transfection with ultrasound destruction of plasmid-bearing cationic microbubbles

Jonathan P. Christiansen, Brent A. French, Alexander L. Klibanov, Sanjiv Kaul, Jonathan Lindner

Research output: Contribution to journalArticle

235 Citations (Scopus)

Abstract

The aim of this study was to assess the relative efficacy and mechanism of gene transfection by ultrasound (US) destruction of plasmid-bearing microbubbles. Luciferase reporter plasmid was charge-coupled to cationic lipid microbubbles. Rat hindlimb skeletal muscle was exposed to intermittent high-power US during dose-adjusted intra-arterial (IA) or IV administration of plasmid-bearing microbubbles via the carotid artery or jugular vein, respectively. At 4 days, luciferase activity in US-exposed skeletal muscle was 200-fold greater with IA than with IV administration of plasmid-bearing microbubbles, and was similar to transfection achieved by IM injection of plasmid (positive control). No transfection occurred with US and IA injection of plasmid alone. Intravital microscopy of the cremaster muscle in mice following administration of microbubbles and US exposure demonstrated perivascular deposition of fluorescent plasmid, the extent of which was twofold greater for IA compared to IV injection. Electron microscopy demonstrated a greater extent of myocellular microporations in US-exposed muscle after IA injection of microbubbles. We conclude that muscle transfection by US destruction of plasmid-bearing cationic microbubbles is amplified by IA, rather than IV, injection of microbubbles due to greater extravascular deposition of plasmid and to greater extent of myocellular microporation.

Original languageEnglish (US)
Pages (from-to)1759-1767
Number of pages9
JournalUltrasound in Medicine and Biology
Volume29
Issue number12
DOIs
StatePublished - Dec 2003
Externally publishedYes

Fingerprint

Microbubbles
plasmids
destruction
Transfection
Plasmids
injection
muscles
Intra-Arterial Injections
skeletal muscle
Luciferases
Injections
Skeletal Muscle
Abdominal Muscles
Muscles
Jugular Veins
Hindlimb
arteries
veins
Carotid Arteries
genes

Keywords

  • Contrast agents
  • Contrast ultrasound
  • Gene delivery
  • Microbubbles
  • Plasmid
  • Ultrasound

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Targeted tissue transfection with ultrasound destruction of plasmid-bearing cationic microbubbles. / Christiansen, Jonathan P.; French, Brent A.; Klibanov, Alexander L.; Kaul, Sanjiv; Lindner, Jonathan.

In: Ultrasound in Medicine and Biology, Vol. 29, No. 12, 12.2003, p. 1759-1767.

Research output: Contribution to journalArticle

Christiansen, Jonathan P. ; French, Brent A. ; Klibanov, Alexander L. ; Kaul, Sanjiv ; Lindner, Jonathan. / Targeted tissue transfection with ultrasound destruction of plasmid-bearing cationic microbubbles. In: Ultrasound in Medicine and Biology. 2003 ; Vol. 29, No. 12. pp. 1759-1767.
@article{5c31a3d1d8a147f0b0273b8a05a1d51c,
title = "Targeted tissue transfection with ultrasound destruction of plasmid-bearing cationic microbubbles",
abstract = "The aim of this study was to assess the relative efficacy and mechanism of gene transfection by ultrasound (US) destruction of plasmid-bearing microbubbles. Luciferase reporter plasmid was charge-coupled to cationic lipid microbubbles. Rat hindlimb skeletal muscle was exposed to intermittent high-power US during dose-adjusted intra-arterial (IA) or IV administration of plasmid-bearing microbubbles via the carotid artery or jugular vein, respectively. At 4 days, luciferase activity in US-exposed skeletal muscle was 200-fold greater with IA than with IV administration of plasmid-bearing microbubbles, and was similar to transfection achieved by IM injection of plasmid (positive control). No transfection occurred with US and IA injection of plasmid alone. Intravital microscopy of the cremaster muscle in mice following administration of microbubbles and US exposure demonstrated perivascular deposition of fluorescent plasmid, the extent of which was twofold greater for IA compared to IV injection. Electron microscopy demonstrated a greater extent of myocellular microporations in US-exposed muscle after IA injection of microbubbles. We conclude that muscle transfection by US destruction of plasmid-bearing cationic microbubbles is amplified by IA, rather than IV, injection of microbubbles due to greater extravascular deposition of plasmid and to greater extent of myocellular microporation.",
keywords = "Contrast agents, Contrast ultrasound, Gene delivery, Microbubbles, Plasmid, Ultrasound",
author = "Christiansen, {Jonathan P.} and French, {Brent A.} and Klibanov, {Alexander L.} and Sanjiv Kaul and Jonathan Lindner",
year = "2003",
month = "12",
doi = "10.1016/S0301-5629(03)00976-1",
language = "English (US)",
volume = "29",
pages = "1759--1767",
journal = "Ultrasound in Medicine and Biology",
issn = "0301-5629",
publisher = "Elsevier USA",
number = "12",

}

TY - JOUR

T1 - Targeted tissue transfection with ultrasound destruction of plasmid-bearing cationic microbubbles

AU - Christiansen, Jonathan P.

AU - French, Brent A.

AU - Klibanov, Alexander L.

AU - Kaul, Sanjiv

AU - Lindner, Jonathan

PY - 2003/12

Y1 - 2003/12

N2 - The aim of this study was to assess the relative efficacy and mechanism of gene transfection by ultrasound (US) destruction of plasmid-bearing microbubbles. Luciferase reporter plasmid was charge-coupled to cationic lipid microbubbles. Rat hindlimb skeletal muscle was exposed to intermittent high-power US during dose-adjusted intra-arterial (IA) or IV administration of plasmid-bearing microbubbles via the carotid artery or jugular vein, respectively. At 4 days, luciferase activity in US-exposed skeletal muscle was 200-fold greater with IA than with IV administration of plasmid-bearing microbubbles, and was similar to transfection achieved by IM injection of plasmid (positive control). No transfection occurred with US and IA injection of plasmid alone. Intravital microscopy of the cremaster muscle in mice following administration of microbubbles and US exposure demonstrated perivascular deposition of fluorescent plasmid, the extent of which was twofold greater for IA compared to IV injection. Electron microscopy demonstrated a greater extent of myocellular microporations in US-exposed muscle after IA injection of microbubbles. We conclude that muscle transfection by US destruction of plasmid-bearing cationic microbubbles is amplified by IA, rather than IV, injection of microbubbles due to greater extravascular deposition of plasmid and to greater extent of myocellular microporation.

AB - The aim of this study was to assess the relative efficacy and mechanism of gene transfection by ultrasound (US) destruction of plasmid-bearing microbubbles. Luciferase reporter plasmid was charge-coupled to cationic lipid microbubbles. Rat hindlimb skeletal muscle was exposed to intermittent high-power US during dose-adjusted intra-arterial (IA) or IV administration of plasmid-bearing microbubbles via the carotid artery or jugular vein, respectively. At 4 days, luciferase activity in US-exposed skeletal muscle was 200-fold greater with IA than with IV administration of plasmid-bearing microbubbles, and was similar to transfection achieved by IM injection of plasmid (positive control). No transfection occurred with US and IA injection of plasmid alone. Intravital microscopy of the cremaster muscle in mice following administration of microbubbles and US exposure demonstrated perivascular deposition of fluorescent plasmid, the extent of which was twofold greater for IA compared to IV injection. Electron microscopy demonstrated a greater extent of myocellular microporations in US-exposed muscle after IA injection of microbubbles. We conclude that muscle transfection by US destruction of plasmid-bearing cationic microbubbles is amplified by IA, rather than IV, injection of microbubbles due to greater extravascular deposition of plasmid and to greater extent of myocellular microporation.

KW - Contrast agents

KW - Contrast ultrasound

KW - Gene delivery

KW - Microbubbles

KW - Plasmid

KW - Ultrasound

UR - http://www.scopus.com/inward/record.url?scp=0345862002&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0345862002&partnerID=8YFLogxK

U2 - 10.1016/S0301-5629(03)00976-1

DO - 10.1016/S0301-5629(03)00976-1

M3 - Article

C2 - 14698343

AN - SCOPUS:0345862002

VL - 29

SP - 1759

EP - 1767

JO - Ultrasound in Medicine and Biology

JF - Ultrasound in Medicine and Biology

SN - 0301-5629

IS - 12

ER -