Liposome-mediated gene transfer in rat lung transplantation: A comparison between the in vivo and ex vivo approaches

Boasquevisque, Carlos Henrique Ribeiro; Mora, Bassem N.; Boglione, Mariano; Ritter, Jon K.; Scheule, Ronald K.; Yew, Nelson S.; DeBruyne, Lisa A.; Qin, Lihui; Bromberg, Jonathan S.; Patterson, G. Alexander

doi:10.1016/s0022-5223(99)70463-0

Cited by 17 publications

(8 citation statements)

References 10 publications

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“…Furthermore, DNA/cationic liposomal complexes have been shown to successfully deliver genes to the lungs after aerosol or intravenous delivery without adverse effects in terms of pulmonary histology, lung compliance, or alveolar-arterial oxygen gradient (23). Because of potential concerns regarding specificity of the phosphorothioate ODN for the chosen target (40,41), scrambled phosphorothioate ODNs, which have identical size and net charge as their parent counterparts-yet do not form heteroduplexes with target mRNA, were used for control conditions (21). In the current studies, only antisense Egr-1 ODN (but not scrambled-sequence Egr-1 ODN) reduced both Egr-1 protein and mRNA levels.…”

Section: Discussionmentioning

confidence: 99%

Extinguishing Egr‐1‐dependent inflammatory and thrombotic cascades following lung transplantation

et al. 2001

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Hypoxic induction of the early growth response-1 (Egr-1) transcription factor initiates proinflammatory and procoagulant gene expression. Orthotopic/isogeneic rat lung transplantation triggers Egr-1 expression and nuclear DNA binding activity corresponding to Egr-1, which leads to increased expression of downstream target genes such as interleukin-1b, tissue factor, and plasminogen activator inhibitor-1. The devastating functional consequences of Egr-1 up-regulation in this setting are prevented by treating donor lungs with a phosphorothioate antisense oligodeoxyribonucleotide directed against the Egr-1 translation initiation site, which blocks expression of Egr-1 and its gene targets. Post-transplant graft leukostasis, inflammation, and thrombosis are consequently diminished, with marked improvement in graft function and recipient survival. Blocking expression of a proximal transcription factor, which activates deleterious inflammatory and coagulant effector mechanisms, is an effective molecular strategy to improve organ preservation.

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Section: Discussionmentioning

confidence: 99%

Extinguishing Egr‐1‐dependent inflammatory and thrombotic cascades following lung transplantation

et al. 2001

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“…7 In mice, intravenous delivery of a reporter gene as DNA-liposome complexes was far more efficient than use of plasmid DNA alone. 36 In a recent study, 37 in which the transfection efficiency of a transforming growth factor-␤ (TGF-␤) cDNA was examined in a rat lung transplant model, the use of the cationic liposomal carrier was shown to increase transfection efficiency up to 4-fold com- A, Effect on graft ICAM-1 protein expression, measured by Western blotting using a primary murine anti-rat ICAM-1 IgG. Samples were taken from fresh (nonpreserved) lungs or from lungs that had been treated with 7 mL of 50 g/mL of either sense (S) or antisense (AS) oligonucleotide (in 50 g/mL of cationic liposomal carrier) administered directly into the left PA at the time of lung harvest.…”

Section: Toda Et Al Antisense Icam-1 In Lung Transplantation 169mentioning

confidence: 95%

Antisense Intercellular Adhesion Molecule-1 (ICAM-1) Oligodeoxyribonucleotide Delivered During Organ Preservation Inhibits Posttransplant ICAM-1 Expression and Reduces Primary Lung Isograft Failure

Toda

Kayano

Karimova

et al. 2000

Circulation Research

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Abstract-Transiently increased expression of leukocyte adhesion receptors after lung preservation contributes to early graft demise by recruiting leukocytes, activating complement, and causing microcirculatory stasis. We hypothesized that inhibiting intercellular adhesion molecule-1 (ICAM-1) expression even briefly may significantly improve lung graft function and that the preservation period might provide a unique window to deliver a therapeutic pulse of antisense oligonucleotide ICAM-1 to inhibit ICAM-1 expression after transplantation. Interleukin-1␤-treated rat pulmonary endothelial cells given a 20-mer phosphorothioate oligonucleotide comprising an antisense span targeted to the 3Ј-untranslated region of rat ICAM-1 demonstrated an oligonucleotide dose-dependent reduction in ICAM-1 expression. Using a cationic liposomal carrier, this same antisense oligonucleotide (but not the sense control) instilled into the pulmonary vasculature at the time of preservation reduced subsequent graft ICAM-1 expression and graft leukostasis and markedly improved oxygenation, pulmonary blood flow, and graft survival. These experiments demonstrate that the preservation period presents a window during which to target an anti-ICAM-1 expression strategy to inhibit early adhesion receptor expression and improve functional outcome after lung transplantation. (Circ Res. 2000;86:166-174.)Key Words: intercellular adhesion molecule-1 Ⅲ lung transplantation Ⅲ isograft Ⅲ leukocyte adhesion receptor C linical lung transplantation at its best is a harrowing experience, because lung grafts can fail catastrophically shortly after reperfusion for reasons that are often not understood. 1,2 Clinical lung preservation strategies are directed toward maintaining proper electrolyte and osmotic homeostasis, but surprisingly little is done to protect the vast pulmonary vascular network on which the lung depends for both integrity and function. Because the early expression of the leukocyte adhesion receptor P-selectin can result in rapid sequestration of neutrophils (polymorphonuclear leukocytes [PMNs]) after lung transplantation, 3 promoting microcirculatory stasis and local tissue destruction, we hypothesized that a strategy that protects the lungs from early leukocyte recruitment could confer clinical benefit. Because P-selectin places neutrophils into a favorable steric relationship for intercellular adhesion molecule-1 (ICAM-1) binding to ␤ 2 -integrins, we hypothesized that early inhibition of inducible ICAM-1 expression might serve as a useful target for therapeutic intervention in lung transplantation to prevent acute graft injury. Toward this end, we have focused on the unique opportunity provided by the lung harvest procedure, during which it is possible to deliver agents (such as antisense oligodeoxynucleotides) ex vivo directly into the vasculature, which can block adhesion receptor expression during the first few critical hours after reperfusion. The current studies were designed to (1) elucidate the nature and functional relevance of endo...

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“…Fibroblasts transfected in vitro with an epidermal growth factor gene have been used successfully for wound healing (22). Experiments have also been performed with vein grafts (23), donor hearts (24), pulmonary artery segments (25), and lung transplants (26). Although in various transfection protocols a portion of the DNA is liberated into the cytoplasm (27), the endocytic route of internalization of nonviral vectors with subsequent degradation of the delivered DNA by lysosomal nucleases brings an additional problem.…”

mentioning

confidence: 99%

Cell transfection in vitro and in vivo with nontoxic TAT peptide-liposome–DNA complexes

Torchilin

Levchenko

Rammohan

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

424

255

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Liposome-mediated gene transfer in rat lung transplantation: A comparison between the in vivo and ex vivo approaches

Abstract: (1) With current liposome technology, the ex vivo route is superior to the in vivo approach; (2) cDNA alone does not provide transgene expression at levels to produce a functional effect.

Cited by 17 publications

References 10 publications

Extinguishing Egr‐1‐dependent inflammatory and thrombotic cascades following lung transplantation

Extinguishing Egr‐1‐dependent inflammatory and thrombotic cascades following lung transplantation

Antisense Intercellular Adhesion Molecule-1 (ICAM-1) Oligodeoxyribonucleotide Delivered During Organ Preservation Inhibits Posttransplant ICAM-1 Expression and Reduces Primary Lung Isograft Failure

Cell transfection in vitro and in vivo with nontoxic TAT peptide-liposome–DNA complexes

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