Harnessing CRISPR/Cas9 Technology for Precision Drug Delivery in Genetic Disorders

Abstract

The convergence of genome editing technologies with advanced drug delivery systems has opened new avenues for the treatment of genetic disorders. Among these technologies, CRISPR/Cas9 has emerged as a revolutionary tool due to its ability to induce precise, site-specific modifications in the genome. This system leverages a guide RNA to direct the Cas9 endonuclease to targeted DNA sequences, enabling gene disruption, correction, or insertion with unprecedented accuracy. While its potential for treating monogenic and complex genetic diseases is immense, a major bottleneck remains the safe and efficient delivery of CRISPR components to the desired cells or tissues in vivo.

This review explores recent advancements in utilizing CRISPR/Cas9 not only as a genome editing tool but as an integral component of precision drug delivery strategies. We assess a variety of delivery platforms—including viral vectors, lipid nanoparticles, gold nanoparticles, and exosome-based systems—that facilitate targeted and controlled administration of CRISPR machinery. The integration of these platforms with CRISPR technology is particularly promising for overcoming biological barriers, enhancing cellular uptake, and reducing off-target effects, all of which are critical for therapeutic translation.

Furthermore, we highlight key preclinical and clinical studies demonstrating successful correction of genetic defects in diseases such as sickle cell anemia, Duchenne muscular dystrophy, and cystic fibrosis. Emphasis is placed on the strategies that optimize specificity, minimize immune responses, and improve tissue targeting. Challenges such as delivery efficiency, off-target mutations, immunogenicity, and ethical considerations are discussed in depth, along with emerging solutions like base editing and prime editing that aim to further refine this therapeutic modality.

Overall, this paper underscores the transformative potential of CRISPR/Cas9-based precision drug delivery systems in the field of genomic medicine. As delivery technologies continue to evolve, and gene-editing tools become increasingly sophisticated, the path toward safe, effective, and personalized therapies for a wide range of genetic disorders becomes more attainable.

DOI: 10.8612/39.4.2024.3