We have recently reported that cell-penetrating peptides (CPPs) and novel chimeric peptides containing CPP (referred as
B peptide) and muscle-targeting peptide (referred as MSP) motifs significantly improve the systemic exon-skipping activity
of morpholino phosphorodiamidate oligomers (PMOs) in dystrophin-deficient mdx mice. In the present study, the general
mechanistic significance of the...
Xenobiotic exposures may induce alternative splicing in the pre-mRNA of nuclear hormone receptor (NHR) genes, yielding unpredictable patterns of gene expression that may promote adverse drug events and promote environmental disease. Informed by observations in the androgen receptor (AR; class I NHR), whereby alternatively-spliced AR transcripts induce ligand-independent hormone signaling...
We have recently reported that cell-penetrating peptides (CPPs) and novel chimeric peptides containing CPP (referred as
B peptide) and muscle-targeting peptide (referred as MSP) motifs significantly improve the systemic exon-skipping activity
of morpholino phosphorodiamidate oligomers (PMOs) in dystrophin-deficient mdx mice. In the present study, the general
mechanistic significance of the...
Full Text:
Dependent Effects of Chimeric Peptide Morpholino Conjugates Contribute to Dystrophin Exon-skipping
We have recently reported that cell-penetrating peptides (CPPs) and novel chimeric peptides containing CPP (referred as
B peptide) and muscle-targeting peptide (referred as MSP) motifs significantly improve the systemic exon-skipping activity
of morpholino phosphorodiamidate oligomers (PMOs) in dystrophin-deficient mdx mice. In the present study, the general
mechanistic significance of the...
Antisense oligonucleotide (AO)-mediated exon-skipping therapeutics shows great promise in correcting frame-disrupting mutations in the DMD gene for Duchenne muscular dystrophy. However, insufficient systemic delivery limits clinical adoption. Previously, we showed that a glucose/fructose mixture augmented AO delivery to muscle in mdx mice. Here, we evaluated if fructose alone could enhance...
Full Text:
presented as fold change relative to saline. (c) RT-PCR
analysis to detect dystrophin exon-skipping
Antisense oligonucleotide (AO)-mediated exon-skipping therapeutics shows great promise in correcting frame-disrupting mutations in the DMD gene for Duchenne muscular dystrophy. However, insufficient systemic delivery limits clinical adoption. Previously, we showed that a glucose/fructose mixture augmented AO delivery to muscle in mdx mice. Here, we evaluated if fructose alone could enhance...
Full Text:
oligonucleotide
(AO)-mediated exon-skipping therapeutics is promising for
DMD patients based on encouraging
Antisense oligonucleotide (AO)-mediated exon-skipping therapeutics shows great promise in correcting frame-disrupting mutations in the DMD gene for Duchenne muscular dystrophy. However, insufficient systemic delivery limits clinical adoption. Previously, we showed that a glucose/fructose mixture augmented AO delivery to muscle in mdx mice. Here, we evaluated if fructose alone could enhance...
Exon skipping is capable of correcting frame-shift and nonsense mutations of
Duchenne Muscular Dystrophy (DMD). Phase II clinical trials in UK and Netherlands
have reported induction of dystrophin expression in muscles of DMD patients by
systemic administrations of both phosphorodiamidate morpholino oligomers (PMO)
and 2’O methyl phosphorothioate. Peptide-conjugated PMO (PPMO)...
Antisense morpholino oligomers are synthetic macromolecules can modify gene expression. While these compounds have great potential to treat a broad range of human diseases, they suffer from poor cellular delivery. Conjugating cell-penetrating peptides onto these morpholinos is one option of addressing delivery, however development remains slow due to the cost...
The BRAF proto-oncogene is a member of the Raf protein family that encodes serine/threonine protein kinases, which activate the MEK/ERK signaling transduction pathway. The V600E mutation of BRAF, found in 70% of melanoma cases, causes an upregulation of MEK/ERK signaling which leads to many hallmarks of cancer, including apoptosis evasion,...