Sequence: Ac-RXRRBRRXRYQFLIRXRBRXRB (Pip6a; X = 6-aminohexanoic acid, B = beta-alanine)
| Experiment Id | EXP002445 |
|---|---|
| Paper | Cell-penetrating peptide-conjugated, splice-switching oligonucleotides mitigate the phenotype in Btk |
| Peptide | Pip6a-PMO 186 |
| Delivery Success Class | yes |
| In Vivo Flag | yes |
| Uptake Confirmed | no |
| Label Confidence | high |
| In Vitro Functional Effect | |
| Endosomal Escape Evidence | |
| Peptide Concentration | 10 mg kg⁻¹ for phenotypic rescue study; 1, 4, and 12 mg kg⁻¹ in dose-finding |
| Rna Concentration | |
| Mixing Ratio | |
| Formulation Format | covalent peptide-oligonucleotide conjugate |
| Formulation Components | Pip6a cell-penetrating peptide + PMO SSO 186 |
| Size Nm | |
| Zeta Mv | |
| Model Scope | in_vivo |
| Model Type | in vivo |
| Cell Lines Or Primary Cells | |
| Animal Model | BAC transgenic Btk/Tec double-deficient XLA mouse model; BAC transgenic dose-finding mice |
| Administration Route | intravenous infusion / intravenous injection |
| Output Type | in vivo splice correction, BTK restoration, and partial phenotypic rescue |
| Output Value | Repeated 10 mg kg⁻¹ dosing twice weekly for 3 weeks partly restored B-lineage phenotype; BTK protein restored; splenic marginal-zone B-cell phenotype and follicular architecture partially normalized; ProB cKit+ and pre-B cells increased in bone marrow |
| Output Units | |
| Output Notes | delivery_success_class = 1 because functional in vivo splice correction and phenotypic rescue were demonstrated, not merely uptake |
| Toxicity Notes | delivery_success_class = 1 because systemic Pip6a-PMO 186 treatment produced in vivo splice correction/BTK restoration and partial phenotypic rescue; exact Pip6a and PMO 186 sequences updated from supplementary information |
| Curation Notes |