Delivery of Intercellular Adhesion Molecule-1 Antisense Oligonucleotides Using a Topical Hydrogel Tissue Sealant in a Murine Partial Nephrectomy/Ischemia Model

Hardeep Phull, Yeong Hau H Lien, Mohamed W. Salkini, Christina Escobar, Li-Wen Lai, Sanjay Ramakumar

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objectives: Ischemia/reperfusion injury is a leading cause of renal damage which can be improved with antisense oligonucleotide gene therapy. We have shown that polyethylene glycol (PEG) hydrogel, which also functions as a tissue sealant, is an effective topical delivery vehicle for oligonucleotides in a murine partial nephrectomy model. The objective of this study was to use and evaluate this method against intercellular adhesion molecule-1 (ICAM-1) to prevent tissue damage. Methods: Sixty mice underwent left upper pole partial nephrectomy with 45 minutes of warm ischemia, randomized to treatment with 50 μg ICAM-1 antisense oligonucleotides embedded in PEG hydrogel, no therapy, or sham surgery. Kidneys were harvested at 24 hours and 3, 4, and 5 days. The specimens were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) for ICAM-1 messenger ribonucleic acid (mRNA), immunohistochemical staining for ICAM-1 protein, and standard histology. Results: At 24 hours, qRT-PCR and immunohistochemistry data showed a significant reduction in ICAM-1 mRNA and protein expression in the antisense group versus the ischemia group, but no difference at 3 to 5 days. Histologically there was reduced inflammation and necrosis in the cortex at 24 hours. The outer and inner medulla also showed improvement at 3 to 5 days in the antisense group as opposed to the ischemia group. Conclusions: Topical PEG hydrogel delivery of antisense ICAM-1 oligonucleotides demonstrated decreased ICAM-1 mRNA expression, reduced ICAM-1 protein staining, and decreased cellular damage. The application of gene therapy through this novel topical delivery system holds potential for a highly specific, localized method of preventing tissue damage after ischemia/reperfusion injury.

Original languageEnglish (US)
Pages (from-to)690-695
Number of pages6
JournalUrology
Volume72
Issue number3
DOIs
StatePublished - Sep 2008

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Antisense Oligonucleotides
Hydrogel
Intercellular Adhesion Molecule-1
Nephrectomy
Ischemia
RNA
Reperfusion Injury
Oligonucleotides
Genetic Therapy
Real-Time Polymerase Chain Reaction
Staining and Labeling
Kidney
Warm Ischemia
Proteins
Histology
Necrosis
Immunohistochemistry
Inflammation
Therapeutics

ASJC Scopus subject areas

  • Urology

Cite this

Delivery of Intercellular Adhesion Molecule-1 Antisense Oligonucleotides Using a Topical Hydrogel Tissue Sealant in a Murine Partial Nephrectomy/Ischemia Model. / Phull, Hardeep; Lien, Yeong Hau H; Salkini, Mohamed W.; Escobar, Christina; Lai, Li-Wen; Ramakumar, Sanjay.

In: Urology, Vol. 72, No. 3, 09.2008, p. 690-695.

Research output: Contribution to journalArticle

Phull, Hardeep ; Lien, Yeong Hau H ; Salkini, Mohamed W. ; Escobar, Christina ; Lai, Li-Wen ; Ramakumar, Sanjay. / Delivery of Intercellular Adhesion Molecule-1 Antisense Oligonucleotides Using a Topical Hydrogel Tissue Sealant in a Murine Partial Nephrectomy/Ischemia Model. In: Urology. 2008 ; Vol. 72, No. 3. pp. 690-695.
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