Abstract

Obesity and metabolic syndrome are multifactorial conditions characterized by dysregulated energy 
metabolism, insulin resistance, chronic inflammation, and increased risk of diabetes and cardiovascular disease. 
Conventional pharmacological treatments often provide modest benefits and suffer from limited durability. Gene 
therapy has emerged as a transformative approach to correct the underlying molecular defects driving these 
disorders. However, effective delivery of genetic material such as DNA, mRNA, siRNA, and miRNA which 
remains a formidable challenge due to degradation, poor cellular uptake, and off-target effects. Nanoparticles 
offer versatile delivery platforms that protect genetic cargo, improve biodistribution, and enable tissue-specific 
targeting. Recent studies demonstrate that nanoparticle-based gene therapy can modulate pathways such as 
adipogenesis, lipolysis, insulin signaling, and appetite regulation, producing sustained metabolic improvements 
in preclinical models. This review explores the principles of nanoparticle-mediated gene therapy, recent 
advances in obesity and metabolic syndrome research, translational barriers, clinical perspectives, and future 
directions. Nanoparticle-enabled gene therapy holds immense potential, but long-term safety, large-scale 
production, and regulatory approval remain significant hurdles before clinical application. 
Keywords: Obesity, Metabolic syndrome, Gene therapy, Nanoparticles, Nucleic acids