Document Detail

Polyethylenimine-modified pluronics (PCMs) improve morpholino oligomer delivery in cell culture and dystrophic mdx mice.
MedLine Citation:
PMID:  23164938     Owner:  NLM     Status:  MEDLINE    
We investigated a series of small-sized polyethylenimine (PEI, 0.8/1.2 k)-conjugated pluronic copolymers (PCMs) for their potential to enhance delivery of an antisense phosphorodiamidate morpholino oligomer (PMO) in vitro and in dystrophic mdx mice. PCM polymers containing pluronics of molecular weight (Mw) ranging 2-6 k, with hydrophilic-lipophilic balance (HLB) 7-23, significantly enhanced PMO-induced exon-skipping in a green fluorescent protein (GFP) reporter-based myoblast culture system. Application of optimized formulations of PCMs with PMO targeted to dystrophin exon 23 demonstrated a significant increase in exon-skipping efficiency in dystrophic mdx mice. Consistent with our observations in vitro, optimization of molecular size and the HLB of pluronics are important factors for PCMs to achieve enhanced PMO delivery in vivo. Observed cytotoxicity of the PCMs was lower than Endo-porter and PEI 25 k. Tissue toxicity of PCMs in muscle was not clearly detected with the concentrations used, indicating the potential of the PCMs as effective and safe PMO carriers for treating diseases such as muscular dystrophy.
Mingxing Wang; Bo Wu; Peijuan Lu; Caryn Cloer; Jay D Tucker; Qilong Lu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-11-20
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  21     ISSN:  1525-0024     ISO Abbreviation:  Mol. Ther.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-07-23     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  210-6     Citation Subset:  IM    
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MeSH Terms
Base Sequence
Cell Line
Genes, Reporter
Green Fluorescent Proteins / genetics
Injections, Intramuscular
Mice, Inbred mdx
Morpholinos / administration & dosage*
Myoblasts / metabolism
Polyethyleneimine / chemistry*
Polymerase Chain Reaction
Reg. No./Substance:
0/Morpholinos; 106392-12-5/Poloxamer; 147336-22-9/Green Fluorescent Proteins; 9002-98-6/Polyethyleneimine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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