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EXP001491

Paper

Combination of valproic acid and morpholino splice-switching oligonucleotide produces improved outcomes in spinal muscular atrophy patient-derived fibroblasts (2017)

Peptide

ApoE (co-treated with VPA)

Sequence: Ac-LRKLRKRLLRXC-NH2 (X = unspecified spacer as shown in paper schematic)

RNA

splice-switching PMO (morpholino)

All experiment fields

Experiment Id EXP001491
Paper Combination of valproic acid and morpholino splice-switching oligonucleotide produces improved outco
Peptide ApoE (co-treated with VPA)
Delivery Success Class no
In Vivo Flag no
Uptake Confirmed no
Label Confidence high
In Vitro Functional Effect yes
Endosomal Escape Evidence
Peptide Concentration ApoE-PMO 0.5–1 µM; VPA 1–10 mM (co-treatment)
Rna Concentration ApoE-PMO 0.5–1 µM
Mixing Ratio N/A (co-administration; not covalent)
Formulation Format co-treatment (small molecule + CPP–PMO)
Formulation Components Valproic acid (VPA) + ApoE-PMO
Size Nm
Zeta Mv
Model Scope in_vitro
Model Type in vitro
Cell Lines Or Primary Cells SMA Type I patient-derived fibroblasts (GM03813, Coriell)
Animal Model
Administration Route
Output Type SMN2 splice switching (RT-qPCR) and SMN protein (western blot)
Output Value Enhanced exon 7 inclusion vs either agent alone (e.g., FL-SMN2 up to ~1.89-fold at 4 h; ~2-fold at 16 h; SMN protein up to ~2.2-fold)
Output Units
Output Notes Co-treatment improved splice switching: 10 mM VPA + 1 µM ApoE-PMO (4 h) gave the only statistically significant FL-SMN2 increase reported for 4 h (~1.89-fold). Over 16 h, 2 mM VPA + ApoE-PMO gave ~2-fold FL-SMN2 increase and increased SMN protein (max reported ~2.2-fold with 2 mM VPA + 0.5 µM ApoE-PMO).
Toxicity Notes Co-treatment generally well tolerated; 5 mM VPA + ApoE-PMO over 16 h reduced viability to ~82% (reported).
Curation Notes