Publication: Peptide-morpholino conjugate: A promising therapeutic for duchenne muscular dystrophy
Issued Date
2009-09-01
Resource Type
ISSN
17496632
00778923
00778923
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2-s2.0-70349453645
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Mahidol University
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SCOPUS
Bibliographic Citation
Annals of the New York Academy of Sciences. Vol.1175, (2009), 55-60
Suggested Citation
Hong M. Moulton, Bo Wu, Natee Jearawiriyapaisarn, Peter Sazani, Qi Long Lu, Ryszard Kole Peptide-morpholino conjugate: A promising therapeutic for duchenne muscular dystrophy. Annals of the New York Academy of Sciences. Vol.1175, (2009), 55-60. doi:10.1111/j.1749-6632.2009.04976.x Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/27085
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Title
Peptide-morpholino conjugate: A promising therapeutic for duchenne muscular dystrophy
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Abstract
Steric-blocking oligos can correct reading frame errors or skip premature termination codons. For Duchenne muscular dystrophy (DMD), systemic administration of oligos produces limited delivery into muscle cells. Conjugation to a cell-penetrating peptide greatly enhances muscle uptake of morpholino oligos. A peptide-morpholino conjugate (PPMO) restored dystrophin in mdx mice to > 80% and 50% of normal levels in skeletal and cardiac muscles, respectively, after a single intravenous 30-mg/kg injection. Six injections over 3 months restored dystrophin to nearly normal levels in all muscles. One PPMO injection daily at 12 mg/kg each for 4 days caused exon skipping clearly detectable in the muscles of the mdx mice 9 weeks later, showing prolonged activity. PPMO significantly improved muscle pathology, strength and function, and the survival rate of mice whose hearts were challenged by chemical-induced heart failure. No toxicity or immunogenicity was detected. Our studies demonstrated that muscle functions can be restored with a low dose of PPMO, making it a promising therapeutic for DMD. © 2009 New York Academy of Sciences.