Hong M. MoultonBo WuNatee JearawiriyapaisarnPeter SazaniQi Long LuRyszard KoleAVI BioPharma IncorporatedCarolinas Medical CenterMahidol University2018-09-132018-09-132009-09-01Annals of the New York Academy of Sciences. Vol.1175, (2009), 55-6017496632007789232-s2.0-70349453645https://repository.li.mahidol.ac.th/handle/20.500.14594/27085Steric-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.Mahidol UniversityArts and HumanitiesBiochemistry, Genetics and Molecular BiologyConference PaperSCOPUS10.1111/j.1749-6632.2009.04976.x