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EXP001686

Paper

Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-derived cells and mice (2019)

Peptide

Pip6a-PMO-CAG7

Sequence: Not reported in main text (Pip6a described as hydrophobic core flanked by arginine-rich domains with β-alanine and aminohexanoyl spacers).

RNA

PMO (morpholino antisense oligonucleotide)

All experiment fields

Experiment Id EXP001686
Paper Peptide-conjugated oligonucleotides evoke long-lasting myotonic dystrophy correction in patient-deri
Peptide Pip6a-PMO-CAG7
Delivery Success Class yes
In Vivo Flag yes
Uptake Confirmed yes
Label Confidence high
In Vitro Functional Effect
Endosomal Escape Evidence
Peptide Concentration Dose: 12.5 mg/kg Pip6a-PMO per injection (1–3 injections; analysis at 2 weeks; durability to 6 months)
Rna Concentration Same as dose (conjugate)
Mixing Ratio Covalent conjugate (1:1 peptide:PMO)
Formulation Format Peptide–PMO conjugate (Pip6a-PMO)
Formulation Components Pip6a peptide covalently conjugated to PMO-CAG7 (or Pip6a-Ctrl control sequence)
Size Nm
Zeta Mv
Model Scope in_vivo
Model Type in vivo
Cell Lines Or Primary Cells
Animal Model HSA-LR myotonic dystrophy mouse model (250 CTG repeats in HSA transgene)
Administration Route Intravenous (tail vein)
Output Type in vivo splice correction + phenotypic rescue
Output Value Near-complete correction of DM1 splicing defects (Clcn1 exon 7a, Mbnl1 exon 5, Atp2a1 exon 22) after 2–3 injections (12.5 mg/kg) and complete abolition of myotonia; effects persisted up to ~6 months.
Output Units
Output Notes HSA-LR mice received IV (tail vein) injections: single 12.5 mg/kg (partial correction) and 2–3 injections 12.5 mg/kg (almost complete/full correction). Functional myotonia assay normalized; transcriptomic and proteomic shifts toward WT reported.
Toxicity Notes Mild liver/kidney histological changes at 2 weeks mostly reversed by 6 months; described as transient/reversible.
Curation Notes