PEGylated enhanced cell penetrating peptide nanoparticles for lung gene therapy.

Journal of Controlled Release : Official Journal of the Controlled Release Society
Gizem OsmanJames E Dixon

Abstract

The lung remains an attractive target for the gene therapy of monogenetic diseases such as cystic fibrosis (CF). Despite over 27 clinical trials, there are still very few gene therapy vectors that have shown any improvement in lung function; highlighting the need to develop formulations with improved gene transfer potency and the desirable physiochemical characteristics for efficacious therapy. Herein, we introduce a novel cell penetrating peptide (CPP)-based non-viral vector that utilises glycosaminoglycan (GAG)-binding enhanced transduction (GET) for highly efficient gene transfer. GET peptides couple directly with DNA through electrostatic interactions to form nanoparticles (NPs). In order to adapt the GET peptide for efficient in vivo delivery, we engineered PEGylated versions of the peptide and employed a strategy to form DNA NPs with different densities of PEG coatings. We were able to identify candidate formulations (PEGylation rates ≥40%) that shielded the positively charged surface of particles, maintained colloidal stability in bronchoalveolar lavage fluid (BALF) and retained gene transfer activity in human bronchial epithelial cell lines and precision cut lung slices (PCLS) in vitro. Using multiple particle tracking ...Continue Reading

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Methods Mentioned

BETA
transfection
bronchoalveolar lavage
lavage
flow cytometry
transfect
fluorescence microscopy
dynamic light scattering
Assay
Protein Assay

Software Mentioned

ImageJ
WEASEL
Prism
GraphPad
Matrix Laboratory ( MATLAB )
MTP
GET

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