Endosomolytic Peptides Enable the Cellular Delivery of Peptide Nucleic Acids.
JoLynn B GiancolaRonald T RainesPublished in: bioRxiv : the preprint server for biology (2024)
Precision genetic medicine enlists antisense oligonucleotides (ASOs) to bind to nucleic acid targets important for human disease. Peptide nucleic acids (PNAs) have many desirable attributes as ASOs but lack cellular permeability. Here, we use an assay based on the corrective splicing of an mRNA to assess the ability of synthetic peptides to deliver a functional PNA into a human cell. We find that the endosomolytic peptides L17E and L17ER 4 are highly efficacious delivery vehicles. Co-treatment of a PNA with low micromolar L17E or L17ER 4 enables robust corrective splicing in nearly all treated cells. Peptide-PNA conjugates are even more effective. These results enhance the utility of PNAs as research tools and potential therapeutic agents.
Keyphrases
- nucleic acid
- endothelial cells
- induced pluripotent stem cells
- induced apoptosis
- amino acid
- pluripotent stem cells
- estrogen receptor
- high throughput
- breast cancer cells
- gene expression
- endoplasmic reticulum
- genome wide
- cell cycle arrest
- cell therapy
- cell death
- oxidative stress
- bone marrow
- binding protein
- dna methylation
- signaling pathway
- pi k akt