Lipid nanoparticles (LNPs) have emerged as a critical advancement in CRISPR-Cas9 genome editing, offering efficient and targeted delivery of nucleic acid-based therapies. This review highlights the role of LNPs in overcoming challenges associated with CRISPR-Cas9 delivery, including low transfection efficiency, off-target effects, and poor stability. LNPs, composed of lipids and nucleic acids, provide a protective environment for CRISPR components, enhancing their cellular uptake and reducing immune responses. They are particularly effective in delivering CRISPR-Cas9 in various formats, such as plasmid DNA (pDNA), mRNA, and ribonucleoprotein (RNP) complexes. The review discusses the molecular mechanisms of CRISPR-Cas9, current delivery strategies, and the advantages of LNPs in improving genome editing efficiency. It also covers recent clinical trials and future directions for LNPs in therapeutic applications, emphasizing their potential in treating genetic diseases, infectious diseases, and cancer. LNPs have shown promise in delivering CRISPR-Cas9 for gene therapy, animal model generation, and vaccine development, with significant advancements in mRNA-based vaccines like those for COVID-19. The review underscores the importance of optimizing LNP formulations for tissue-specific delivery and reducing off-target effects, paving the way for their broader clinical application.Lipid nanoparticles (LNPs) have emerged as a critical advancement in CRISPR-Cas9 genome editing, offering efficient and targeted delivery of nucleic acid-based therapies. This review highlights the role of LNPs in overcoming challenges associated with CRISPR-Cas9 delivery, including low transfection efficiency, off-target effects, and poor stability. LNPs, composed of lipids and nucleic acids, provide a protective environment for CRISPR components, enhancing their cellular uptake and reducing immune responses. They are particularly effective in delivering CRISPR-Cas9 in various formats, such as plasmid DNA (pDNA), mRNA, and ribonucleoprotein (RNP) complexes. The review discusses the molecular mechanisms of CRISPR-Cas9, current delivery strategies, and the advantages of LNPs in improving genome editing efficiency. It also covers recent clinical trials and future directions for LNPs in therapeutic applications, emphasizing their potential in treating genetic diseases, infectious diseases, and cancer. LNPs have shown promise in delivering CRISPR-Cas9 for gene therapy, animal model generation, and vaccine development, with significant advancements in mRNA-based vaccines like those for COVID-19. The review underscores the importance of optimizing LNP formulations for tissue-specific delivery and reducing off-target effects, paving the way for their broader clinical application.