Abstract
Nucleic acid (NA) therapy holds tremendous potential for treating a wide range of genetic diseases by the delivery of therapeutic genes into target cells. However, significant challenges exist in safely and effectively delivering these genes to their intended locations. Viral vectors, though efficient, pose risks such as immunogenicity and mutagenesis. This has resulted in growing interest in non-viral, nanoparticle-based NA delivery systems. This review article describes various physiological barriers to NA delivery and explores nanoparticle-based NA delivery systems, including bioengineered nanoparticles, peptides, lipid nanoparticles, and polymeric nanoparticles, highlighting their unique features to overcome in vivo barriers for NA delivery. While these nanoparticle-based NA delivery systems offer a promising alternative to viral vectors, challenges related to cytotoxicity, reproducible synthesis, and cost need to be addressed. The current clinical landscape of NA delivery is also discussed, emphasizing the need for safer, scalable, and cost-effective solutions. Nanoparticles represent a promising future in NA therapy, with the possibility of developing clinically relevant, non-toxic, stable, and non-immunogenic delivery vehicles, paving the way for broader therapeutic applications and improved clinical outcomes.