Crispr-Based Drug Delivery and Therapeutics in Gene Therapy: A Comprehensive Review

The Aim of this article is to review CRISPR-based drug delivery systems and their therapeutic applications in gene therapy, focusing on advancements, challenges, and future prospects. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology has emerged as a transformative tool in gene therapy, enabling precise and efficient genome editing with unprecedented ease compared to earlier platforms such as zinc finger nucleases and TALENs. By leveraging the Cas nuclease system, CRISPR enables targeted modification of disease-causing genes, offering promising therapeutic interventions for genetic disorders, cancers, and infectious diseases. However, the clinical translation of CRISPR-based therapeutics critically depends on the development of safe, efficient, and tissue-specific delivery systems. Current strategies encompass viral vectors (e.g., adeno-associated viruses, lentiviruses) and non-viral carriers (e.g., lipid nanoparticles, polymeric systems, cell-penetrating peptides), each with unique advantages and limitations in terms of delivery efficiency, cargo capacity, immunogenicity, and off-target effects. Advances in nanotechnology and biomaterials have further enabled targeted and stimuli-responsive delivery, enhancing therapeutic precision while minimizing systemic toxicity. Furthermore, CRISPR-based modalities such as base editing, prime editing, and CRISPR interference/activation expand the therapeutic landscape beyond simple gene knockout or repair. Despite remarkable progress, challenges remain in optimizing delivery to specific tissues, controlling off-target activity, and addressing ethical and regulatory concerns. This review provides a comprehensive overview of CRISPR-based drug delivery systems, recent preclinical and clinical advancements, and future perspectives in gene therapy, emphasizing innovations that bridge the gap between experimental success and clinical application.