In vivo delivery of nucleic acids via glycopolymer vehicles affords therapeutic infarct size reduction in vivo Journal Article

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Authors: Tranter, M.; Liu, Y; He, S.; Gulick, J.; Ren, X; Robbins, J.; Jones, W. K.; Reineke, T. M.
Article Title: In vivo delivery of nucleic acids via glycopolymer vehicles affords therapeutic infarct size reduction in vivo
Abstract: Using a new class of nontoxic and degradable glycopolymer-based vehicles termed poly(glycoamidoamine)s, we demonstrate virus-like delivery efficacy of oligodeoxynucleotide (ODN) decoys to cardiomyoblasts (H9c2), primary cardiomyocytes, and the mouse heart. These glycopolymers bind and compact ODN decoys into nanoparticle complexes that are internalized by the cell membrane and mediate nuclear uptake of DNA in 90+% of cultured primary cardiomyocytes and 87% of the mouse myocardium. Experimental results reveal that decoys delivered via these glycopolymers block the activation of the transcription factor NF-kappaB, a major contributor to ischemia/reperfusion injury. Decoy complexes formed with glycopolymer T4 significantly blocked downstream gene expression of Cox-2 and limited myocardial infarction in vivo, phenocopying a transgenic mouse model. These promising delivery vehicles may facilitate high-throughput genetic approaches in animal models. Additionally, the low toxicity, biodegradation, and outstanding delivery efficacy suggest that these nanomedicines may be clinically applicable for gene regulatory therapy.
Journal Title: Molecular therapy : the journal of the American Society of Gene Therapy
Volume: 20
Issue: 3
ISSN: 1525-0024; 1525-0016
Publisher: Unknown  
Journal Place: United States
Date Published: 2012
Start Page: 601
End Page: 608
Language: eng
DOI/URL:

10.1038/mt.2011.267
Notes: LR: 20140321; GR: HL091478/HL/NHLBI NIH HHS/United States; GR: HL63034/HL/NHLBI NIH HHS/United States; GR: P01HL69779/HL/NHLBI NIH HHS/United States; GR: R21 EB003938/EB/NIBIB NIH HHS/United States; GR: R21EB007244/EB/NIBIB NIH HHS/United States; JID: 100890581; 0 (NF-kappa B); 0 (Nanoconjugates); 0 (Oligodeoxyribonucleotides); 0 (Polymers); OID: NLM: PMC3293615; 2011/12/20 [aheadofprint]; ppublish