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Engineering and visualization of bacteria for targeting infarcted myocardium.


ABSTRACT: Optimization of the specific affinity of cardiac delivery vector could significantly improve the efficiency of gene/protein delivery, yet no cardiac vectors to date have sufficient target specificity for myocardial infarction (MI). In this study, we explored bacterial tropism for infarcted myocardium based on our previous observations that certain bacteria are capable of targeting the hypoxic regions in solid tumors. Out of several Escherichia coli or Salmonella typhimurium strains, the S. typhimurium defective in the synthesis of ppGpp (?ppGpp S. typhimurium) revealed accumulation and selective proliferation in the infarcted myocardium without spillover to noncardiac tissue. The Salmonellae that were engineered to express a variant of Renilla luciferase gene (RLuc8), under the control of the E. coli arabinose operon promoter (P(BAD)), selectively targeted and delivered RLuc8 in the infarcted myocardium only upon injection of L-arabinose. An examination of the infarct size before and after infection, and estimations of C-reactive protein (CRP) and procalcitonin indicated that intravenous injection of ?ppGpp S. typhimurium did not induce serious local or systemic immune reactions. This current proof-of-principle study demonstrates for the first time the capacity of Salmonellae to target infarcted myocardium and to serve as a vehicle for the selective delivery of therapeutic agents in MI.

SUBMITTER: Le UN 

PROVIDER: S-EPMC3098638 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Engineering and visualization of bacteria for targeting infarcted myocardium.

Le Uyenchi N UN   Kim Hyung-Seok HS   Kwon Jin-Sook JS   Kim Mi Yeon MY   Nguyen Vu H VH   Jiang Sheng Nan SN   Lee Byeong-Il BI   Hong Yeongjin Y   Shin Myung Geun MG   Rhee Joon Haeng JH   Bom Hee-Seung HS   Ahn Youngkeun Y   Gambhir Sanjiv S SS   Choy Hyon E HE   Min Jung-Joon JJ  

Molecular therapy : the journal of the American Society of Gene Therapy 20110301 5


Optimization of the specific affinity of cardiac delivery vector could significantly improve the efficiency of gene/protein delivery, yet no cardiac vectors to date have sufficient target specificity for myocardial infarction (MI). In this study, we explored bacterial tropism for infarcted myocardium based on our previous observations that certain bacteria are capable of targeting the hypoxic regions in solid tumors. Out of several Escherichia coli or Salmonella typhimurium strains, the S. typhi  ...[more]

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