COMPARATIVE ANALYSIS OF NON-VIRAL GENE DELIVERY SYSTEMS AND THEIR IMPACT ON CELLULAR UPTAKE AND GENE EXPRESSION EFFICIENCY

Abstract

Non-viral gene delivery systems have become very popular because they are safer and more universal than viral vectors and have various benefits, including decreased immunogenicity, enhanced scalability, and versatile structure. Their extensive use in clinical practice is, however, restricted by poor efficiency in transfection and numerous intracellular obstacles. This paper provides a comparative study carried out in a systematic manner of 3 of the most well-known non-viral gene delivery platforms, such as lipid-based nanoparticles, polymeric carriers, dendrimers, and hybrid nanomaterials, regarding their ability to influence cellular uptake and cellular efficiency of gene delivery. The systematic analysis framework was used to analyze important parameters of physicochemical qualities in terms of particle size, surface charge, and compositional architecture, and their relation to biological performance. Endocytosis, endosomal escape, cytoplasmic transport, and nuclear import are some of the critical steps in delivery that were studied to find out factors that control the transgene expression rate. The results show that lipid-based and hybrid systems are better uptake and expression systems because of the increased association with membrane and an enhanced endosomal escape system whereas polymeric systems show constraints that is related to cytotoxicity and intracellular degradation. Moreover, profound surface engineering approaches like PEGylation and ligand functionalization are important to increase the stability of delivery and specificity in targets. In general, this research offers mechanical explanations and design principles of the optimization of non-viral gene delivery systems, to obtain a better therapeutic effect.