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EXP001991

Paper

Bi-specific splice-switching PMO oligonucleotides conjugated via a single peptide active in a mouse model of Duchenne muscular dystrophy (2015)

Peptide

1:1 cocktail of single Pip6a-PMOs (Dmd + Acvr2b) (in vivo)

Sequence: RXRRBRRXRYQFLIRXRBRXRB

RNA

PMO (phosphorodiamidate morpholino oligomer; splice-switching oligonucleotide)

All experiment fields

Experiment Id EXP001991
Paper Bi-specific splice-switching PMO oligonucleotides conjugated via a single peptide active in a mouse
Peptide 1:1 cocktail of single Pip6a-PMOs (Dmd + Acvr2b) (in vivo)
Delivery Success Class yes
In Vivo Flag yes
Uptake Confirmed no
Label Confidence high
In Vitro Functional Effect
Endosomal Escape Evidence
Peptide Concentration Total 0.5 nmol PMO-conjugate mixture per TA (1:1).
Rna Concentration Two separate PMO conjugates co-delivered.
Mixing Ratio Mixture of two individual P-PMOs at 1:1 molar ratio (Pip6a-PMO(Dmd) + Pip6a-PMO(Acvr2b)).
Formulation Format Covalent CPP–PMO conjugate(s) for in vivo splice switching in muscle (intramuscular administration).
Formulation Components Separate single conjugates mixed prior to injection.
Size Nm
Zeta Mv
Model Scope in_vivo
Model Type in vivo
Cell Lines Or Primary Cells
Animal Model mdx mice (C57BL/10ScSn-Dmdmdx/J); tibialis anterior muscle intramuscular injection
Administration Route Intramuscular injection into TA: 0.5 nmol peptide–PMO in 30 µL 0.9% saline; analysis 2 weeks post-injection
Output Type In vivo functional RNA delivery: exon skipping in TA muscle (RT-PCR + qPCR)
Output Value ~35–40% Dmd exon23 skipped transcripts by qPCR; Acvr2b exon5 skipping present (lower than Dmd).
Output Units
Output Notes Used as comparator; bi-specific constructs show no significant loss of in vivo efficacy versus cocktail.
Toxicity Notes
Curation Notes