Peptide Nanoparticle Delivery of Charge-Neutral Splice-Switching Morpholino Oligonucleotides (2015)
Sequence: Stearoyl-(RXR)4-HHHHH (X=Ahx)
PMO (phosphorodiamidate morpholino oligonucleotide; splice-switching)
| Experiment Id | EXP001006 |
|---|---|
| Paper | Peptide Nanoparticle Delivery of Charge-Neutral Splice-Switching Morpholino Oligonucleotides |
| Peptide | STR4 |
| 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; SMA fibroblast screen (GM03813) with 25-mer PMO at 1 µM |
| Rna Concentration | PMO 1 µM (25-mer) |
| Mixing Ratio | peptide:PMO molar ratio 5:1 |
| Formulation Format | noncovalent lipopeptide/PMO nanoparticles (co-incubation; complex formation) |
| Formulation Components | STR4 + PMO SMA 25-mer (ISS-N1); 5'-AGATTCACTTTCATAATGCTGGCAG-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 | Increased SMN2 exon 7 inclusion vs untreated/naked PMO (screen). |
| Output Units | |
| Output Notes | Screen across lipopeptide classes; ST-RXR4 among the highest within the novel lipopeptide set, but PepFects (PF14/PF6) were overall more potent in SMA. |
| Toxicity Notes | Myotube viability (MTS): no toxicity at working concentration (~5 µM peptide). St-RXR4 showed toxicity at 40 µM (without PMO). |
| Curation Notes |