DNA vs. RNA Editing: A Systematic Review Evaluating CRISPR-Cas9 and CRISPR-Cas13 Therapies for Huntington's Disease

Clustered Regularly Interspaced Short Palindromic Sequences (CRISPR) gene editing has emerged as a viable treatment across various genetic diseases. Since Huntington's disease is a fatal neurodegenerative disorder caused by a single mutation, it is essential to explore CRISPR as a possible treatment option. This review identifies the optimal traits of the CRISPR-Cas9 and CRISPR-Cas13 mechanisms in Huntington's disease, including the CRISPR system, guide design, delivery method, phenotypic and genotypic effects, off-target effects, and treatment safety, while comparing their efficacy. Studies were identified through a systematic search on PubMed and ScienceDirect from 2015 to 2025. Selected studies followed high-quality experimentation, were peer-reviewed, published, and discussed the CRISPR system, guide design, delivery method, off-target effects, safety, and results of the treatment. Trends such as targeting single-nucleotide polymorphisms (SNPs) in exon 1 using CRISPR-Cas9 and preventing the translation of mutant mRNA transcripts in CAG-repeat sequences on the mutant allele with CRISPR-Cas13 were identified. Furthermore, both systems improved phenotypic effects and reduced complications associated with Huntington's disease. Whereas CRISPR-Cas9 causes irreversible edits, the effects of CRISPR-Cas13 are temporary and have been shown to have fewer potential risks by targeting the RNA. However, post-treatment neurogenesis could give rise to new neurons susceptible to Huntington's disease. Overall, more in vivo studies should be conducted to further solidify the results.