Enhancing RNA-Based Technologies Using Enzyme-Derived Lipoamino Acids

This work aims to contribute to nucleic acid therapy advances by highlighting RNA interactions with novel compounds, namely lipoaminoacids (LAAs), which show great potential as non-viral vectors. LAAs not only retain the advantages associated with current non-viral vectors, namely fewer health risks, but also can form stable lipoplexes with genetic material, positioning them as promising candidates for advanced gene delivery systems. The biosynthesis of LAAs, using the enzymes, porcine pancreatic lipase (PPL), and a mixture of PPL and papain, enhanced the production, making them more environmentally friendly with reduced production costs, increasing their interest. Conductivity, absorbance at 260 nm, viscosity, and ethidium bromide fluorescence displacement assays were performed to study the characteristics of these lipoaminoacids and their interactions with nucleic acids (RNA and DNA) regarding a potential vector gene delivery system. The Gibbs energy of micellization of lipoaminoacid biosynthesized with PPL was −27.7 kJ/mol, showing great efficiency in micelle formation. All the obtained lipoaminoacids showed successful encapsulation of RNA, demonstrating the potential of these compounds for vector gene therapy.