Cell-Division-Independent Rapid Expression of DNA Delivered with α-Synuclein–Gold Nanoparticle Conjugates

Gene delivery is a primary technology employed in diverse areas of biomedical science, from gene therapy to gene editing, cancer treatment, and stem cell research. Here, we introduce a gene delivery system utilizing an intrinsically disordered protein of α-synuclein (αS) demonstrated to interact with lipid membranes by transforming its original random structure to an α-helix. Since the helix bundle formation is a signature of cell-penetrating peptides for membrane translocation, a multitude of αS(Y136C)s replacing tyrosine at the C-terminus with cysteine were covalently attached onto gold nanoparticles (AuNPs) in a specific orientation with the helix-forming basic N-termini exposed outward. The resulting αS(Y136C)-AuNP conjugates were found to exhibit a rapid gene expression without causing cytotoxicity when the gene of the enhanced green fluorescent protein (EGFP) was delivered with the…