Abstract

LIPOSOMAL GENE DELIVERY SYSTEMS: A MECHANISTIC FRAMEWORK FOR TARGETED THERAPEUTICS AND NEXT-GENERATION INNOVATIONS

*Uma Rajeswari Madana, K. Srinivasa Reddy, Dr. D. Vinay Kumar, Animireddi Ramayyamma and Gunnam Bhavya Tejaswi

Abstract

Gene therapy stands as a transformative medical paradigm, offering the potential to correct genetic defects and fundamentally alter disease progression where conventional treatments fall short. However, the efficacy of gene therapy is heavily reliant on effective delivery systems, as naked genetic material is unstable, quickly degraded by nucleases, and poorly penetrates cell membranes. While viral vectors exhibit high transfection efficiency, concerns regarding immunogenicity and insertional mutagenesis have spurred the development of non-viral alternatives. Among non-viral methods, liposomal gene delivery systems represent a highly versatile and clinically adaptable platform. First described in the 1960s, liposomes are biocompatible, biodegradable spherical vesicles. They are engineered to encapsulate and protect delicate genetic payloads such as mRNA, siRNA, and DNA plasmids. The mechanism involves the formation of positively charged lipoplexes with cationic lipids, enabling electrostatic interaction with cell membranes and subsequent cellular uptake primarily via endocytosis. Critical to their function is endosomal escape, facilitated by fusogenic lipids like DOPE and pH-sensitive components that destabilize the endosomal membrane in acidic environments. Strategies like PEGylation enhance systemic circulation by reducing clearance, while targeting ligands improve cell-specific delivery.

Keywords: Liposomes, Gene Therapy, Non-viral Vectors, Lipid Nanoparticles (LNPs), mRNA Vaccines, CRISPR/Cas9, Cancer Therapy, Genetic Disorders, Drug Delivery, Targeted Therapeutics, Smart Liposomes, Personalized Medicine, AI in Nano medicine.