A Comparative Analysis of CRISPR-Cas9 and Gene-Lowering Approaches for the Treatment of Huntington’s Disease
DOI:
https://doi.org/10.58445/rars.4095Keywords:
Huntington's disease, CRISPR/Cas9, AAV, gene-lowering, gene-editingAbstract
Huntington’s disease is a severe autosomal dominant inherited disease, which means a person will suffer from this disease even if only one allele is mutated. The disease is caused by CAG trinucleotide repeat expansion in 4th chromosome, HTT gene, and only a little approach could be helpful to treat this disease from now. Today, approximately 5 out of every 100,000 people will suffer from this disease all around the world. This article explores two groundbreaking technologies that emerged at the end of 2025, marking the first time Huntington’s disease has ever been successfully treated. Two rivaling approaches are at play: CRISPR-Cas9 editing of the gene responsible for Huntington’s disease (HTT), and gene-lowering, which involves the degradation of the mRNA produced by miRNA. In previous research, the gene-lowering method functioned in mutant Huntington mRNA, instead of targeting the gene itself. This paper compares the benefits and shortcomings of these two prevailing methods for curing Huntington’s disease. According to this paper, the gene-lowering method is relatively mature, and it is getting increasingly closer to being released in the market as a drug. The CRISPR-Cas 9 method is theoretically more efficient due to its once-and-for-all characteristic, and could be more convenient. However, both treatments are all facing the delivery challenge. This paper provides a comprehensive comparison of two novel approaches for treating Huntington’s disease, providing a roadmap for where this research needs improvement, and may progress in the future.
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