Using CRISPR/Cas9 for Therapeutic Approaches to Alzheimer's Disease

This review summarizes the key aspects of the CRISPR/Cas9 system. CRISPR/Cas9, derived from the genomes of bacteria and archaea, is a gene-editing tool consisting of single-guide RNA and the Cas9 enzyme, with Type II being the most commonly used due to its simplicity. It functions by recognizing target DNA via sgRNA, cutting it with Cas9, and repairing breaks through non-homologous end joining (NHEJ) or homology-directed repair (HDR). In practical, it's widely used in gene engineering, including gene therapy and disease modeling. For Alzheimer's disease (AD), it aids in creating cell and animal models, identifying causal genes like APOE and APP. Delivery systems include viral vectors (e.g., AAVs) and non-viral methods (e.g., nanocomplexes, microvesicles), with intranasal delivery showing promise for AD. However, challenges exist: off-target cleavages due to factors like mismatches, sequence similarities, and GC content; vector issues such as stability, target accumulation, and immune responses; and ethical and safety concerns including irreversible edits and limited long-term studies. Despite this, its feasibility and efficiency drive ongoing research, with future work focusing on improving safety and addressing these challenges.