Effective Nanoparticle‐based Gene Delivery by a Protease Triggered Charge Switch

• DOI: 10.1002/adhm.201300503
• Publication Date: 2014-03-20T18:47:00Z
• Authors: Torben Gjetting; Rasmus Irming Jølck; Thomas Lars Andresen
• Keywords: PEGylation

Gene carriers made from synthetic materials are of interest in relation to gene therapy but suffer lack transfection efficiency upon systemic delivery. To address this problem, a novel lipo‐peptide‐PEG conjugate constituted by lipid‐anchor, peptide sensitive proteases and poly (ethylene glycol) (PEG) chain is investigated. Utilizing ethanol‐mediated nucleic acid encapsulation prepare lipo‐nanoparticles (LNPs), LNPs that stable serum obtained. The constitute highly effective delivery systems vitro possess the right features for further investigation vivo including PEG layer net negative charge should ensure long‐circulating properties before being activated diseased tissue. Protease activation leads detachment switching where become positive due presence glutamates cleaved moiety. cationic lipid DOTAP used mainly complex DNA proton titratable DODAP increase endosomal escape enhance efficiency. idea using mixture permanently charged lipids shielded protease negatively coat appears be efficient solution achieving non‐viral results warrant investigations.