Public Health & Health Science Division, ULAB

Several studies have examined the efficacy of the CRISPR/Cas9 gene-editing tool in remedying the toxic effects of Huntington’s disease (HD) as a potential therapy for preventing the neurodegeneration that is observed in HD. Huntington’s disease is caused by an abnormality in the huntingtin (HTT) gene, which leads to the encoding of the mutant huntingtin protein (mHTT). The accumulation of mHTT protein in neurons has been found to cause oxidative stress and inflammatory pathways. Additionally, the abnormality in the HTT gene has been attributed to the abnormal expansion of a CAG trinucleotide repeat sequence. Therefore, some studies used CRISPR/Cas9 to target the mHTT gene, along with genes that play a role in redox regulation, including Nrf2 and SOD2. The results of this study showed a decrease in oxidative stress and greater mitochondrial function. A second study builds on these findings in recognizing the dangers involved with removing the CAG repeat in the gene. This study tested the use of a single gRNA to selectively remove particular CAG repeats in the mutated HTT gene at the site of transcription. This allele-specific approach changes genetic expression permanently.