Gene targeting techniques for Huntington's disease.

Area of Science:

• Neurodegenerative Disorders
• Genetics
• Molecular Biology

Background:

• Huntington's disease (HD) is an inherited neurodegenerative disorder.
• It stems from expanded CAG repeats in the HTT gene, leading to mutant huntingtin protein (mHTT).
• Wild-type huntingtin protein (HTT) is vital for cellular functions, while mHTT disrupts these processes.

Purpose of the Study:

• To review current and emerging therapeutic strategies for Huntington's disease.
• To explore methods for reducing mutant huntingtin protein (mHTT) expression.
• To assess the potential of novel gene-editing technologies for HD treatment.

Main Methods:

• Review of scientific literature on DNA and RNA targeting strategies for HD.
• Categorization of silencing approaches into non-allele-specific and allele-specific methods.
• Analysis of Single Nucleotide Polymorphisms (SNPs) and haplogrouping for allele-specific silencing.

Main Results:

• Multiple DNA and RNA-based approaches can reduce mHTT expression.
• Non-allele-specific silencing affects all HTT alleles.
• Allele-specific silencing utilizes genetic variations (SNPs) for targeted reduction of mHTT.

Conclusions:

• Targeting DNA and RNA offers promising therapeutic avenues for Huntington's disease.
• Allele-specific silencing presents a refined approach by distinguishing between mutant and wild-type HTT.
• CRISPR prime editing technology shows potential for precise targeting of HD-causing mutations.