Peptide Nanoparticle Delivery of Charge-Neutral Splice-Switching Morpholino Oligonucleotides (2015)
Sequence: Ac-(RXR)4 (X=Ahx) (no lipid)
PMO (phosphorodiamidate morpholino oligonucleotide; splice-switching)
| Experiment Id | EXP001019 |
|---|---|
| Paper | Peptide Nanoparticle Delivery of Charge-Neutral Splice-Switching Morpholino Oligonucleotides |
| Peptide | Ac-RXR4 |
| Delivery Success Class | no |
| In Vivo Flag | no |
| Uptake Confirmed | no |
| Label Confidence | high |
| In Vitro Functional Effect | yes |
| Endosomal Escape Evidence | |
| Peptide Concentration | Formulated as nanoparticles; Lipid-length comparison in H2K mdx myotubes using RXR4 ± lipid (C12–C18) |
| Rna Concentration | PMO 1 µM (DMD ON) |
| Mixing Ratio | peptide:PMO molar ratios varied (2:1–7:1) in lipid-length experiments |
| Formulation Format | noncovalent lipopeptide/PMO nanoparticles (co-incubation; complex formation) |
| Formulation Components | Ac-RXR4 + PMO DMD (M23D; exon 23 skipping); 5'-GGCCAAACCTCGGCTTACCTGAAAT-3' |
| Size Nm | |
| Zeta Mv | |
| Model Scope | in_vitro |
| Model Type | in vitro |
| Cell Lines Or Primary Cells | U2OS stable luciferase reporter (BTK intron XLA model); SMA type I fibroblasts GM03813; H2K mdx myotubes + healthy H2K myotubes |
| Animal Model | |
| Administration Route | |
| Output Type | in vitro splice switching (RT-PCR exon inclusion/skipping; luc reporter splice correction) |
| Output Value | Lipid attachment improved exon 23 skipping vs Ac-RXR4 (no lipid); C12/C14 showed strongest enhancement among tested lipid lengths. |
| Output Units | |
| Output Notes | Shorter lipid tails (C12 lauroyl, C14 myristoyl) formed smaller nanoparticles and produced higher exon-skipping activity than longer C16/C18 tails in this RXR4 series. |
| Toxicity Notes | Myotube viability (MTS): no toxicity at working concentration (~5 µM peptide). St-RXR4 showed toxicity at 40 µM (without PMO). |
| Curation Notes |