CRISPR-Nanoparticle Delivery Systems for Gene Editing of Obesity and Diabetes Targets
Mpora Kakwanzi Evelyn
Department of Pharmacognosy Kampala International University Uganda
Email: evelyne.mpora@studwc.kiu.ac.ug
ABSTRACT
Obesity and type 2 diabetes mellitus (T2DM) are complex polygenic diseases in which environmental factors act on a susceptible genomic background to drive chronic energy imbalance, insulin resistance and β-cell failure. Although current pharmacotherapies improve glycemic control and reduce weight in many patients, they do not correct upstream genetic and epigenetic drivers of disease. CRISPR-based genome editing offers the possibility of durable modification of key metabolic pathways, including brown/beige adipocyte thermogenesis, lipid handling, appetite regulation and pancreatic islet function. However, safe and efficient delivery of CRISPR components to specific metabolic tissues remains a major bottleneck. Nanoparticle platforms like lipid nanoparticles, polymeric carriers, inorganic and hybrid systems are emerging as versatile vehicles for in vivo delivery of CRISPR ribonucleoproteins (RNPs), mRNA and base or prime editors to adipose tissue, liver, skeletal muscle and pancreatic islets. This review discusses the rationale for gene editing in obesity and diabetes, outlines priority genetic targets, and focuses on the design principles and performance of nanoparticle-based CRISPR delivery systems. We highlight preclinical studies that edit genes such as PCSK9, ANGPTL3, Fabp4, Ucp1 regulators and glucoregulatory pathways to improve lipid profiles, insulin sensitivity and body weight in rodent models. Challenges related to tissue specificity, editing efficiency, off-target effects, immunogenicity, manufacturing and ethics are examined, alongside future directions including tissue-tropic nanoparticles, multiplex editing and combinatorial strategies with GLP-1 agonists and lifestyle interventions. By enabling controllable, non-viral delivery of gene editors to metabolic tissues, CRISPR–nanoparticle systems could form the basis of next-generation therapies for obesity-associated diabetes.
Keywords: CRISPR–Cas9; lipid nanoparticles; gene editing; obesity and diabetes; metabolic targets
CITE AS: Mpora Kakwanzi Evelyn (2026). CRISPR-Nanoparticle Delivery Systems for Gene Editing of Obesity and Diabetes Targets. IAA Journal of Applied Sciences 14(1):119-126.