Discovery of peptides for targeted delivery of mRNA lipid nanoparticles to cystic fibrosis lung epithelia
Soto, M. R.; Lewis, M. M.; Leal, J.; Pan, Y.; Mohanty, R. P.; Peng, X.; Dong, T.; Ghosh, D.
Show abstract
For cystic fibrosis (CF) patients, a lung targeted gene therapy would significantly alleviate pulmonary complications associated with morbidity and mortality. However, mucus in the airways and cell entry pose huge delivery barriers for local gene therapy. Here, we used phage display technology to select for and identify mucus- and cell-penetrating peptides against primary human bronchial epithelial cells (pHBECs) from CF patients cultured at air-liquid interface (ALI). At ALI, pHBECs produce mucus and reflect CF disease pathology, making it a clinically relevant model. Using this model, we discovered a lead candidate peptide, and incorporated it into lipid nanoparticles (LNPs) to deliver mRNA to pHBECs and mouse lungs in vivo. Compared to LNPs without our peptide, peptide-LNPs demonstrated 7.8-fold and 4.8-fold higher mRNA expression in vitro and in vivo, respectively. Since gene delivery to pHBECs is a significant challenge, we are encouraged by these results and anticipate that our peptide could be used to successfully deliver CF gene therapies in future work.
Matching journals
The top 13 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Targeted Delivery of Chloroquine to Plasmacytoid Dendritic Cells Enhances Inhibition of the Type I Interferon Response 94%
- Safety and biodistribution of NanoligomersTM targeting SARS-CoV-2 genome for treatment of COVID-19 93%
- Modeling airway dysfunction in asthma using synthetic mucus biomaterials 92%
Similar papers in this journal
- In-vitro and in-vivo Characterization of a Multi-Stage Enzyme-Responsive Nanoparticle-in-Microgel Pulmonary Drug Delivery System 94%
- TLR7 and RIG-I dual-adjuvant loaded nanoparticles drive broadened and synergistic responses in dendritic cells in vitro and generate unique cellular immune responses in influenza vaccination 94%
- Transdermal Delivery of Ultradeformable Cationic Liposomes Complexed with miR211-5p (UCL-211) Stabilizes BRAFV600E+ Melanocytic Nevi 94%
Similar papers in this journal
Similar papers in this journal
- Detailed splenic single-cell biodistribution of phosphatidylglycerol-containing liposomes 92%
- Pharmacokinetic considerations for optimizing inhaled spray-dried pyrazinoic acid formulations 91%
- Mechanistic insights into the activation of lecithin-cholesterol acyltransferase in therapeutic nanodiscs composed of apolipoprotein A-I mimetic peptides and phospholipids 90%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.