QRX-704

QRX-704 is a **novel antisense oligonucleotide (ASO) therapeutic** in preclinical and early research development, designed to treat **Huntington's disease** by modulating the splicing of huntingtin (HTT) pre-mRNA to produce an alternative isoform, known as **HTT Δ12**. This isoform lacks exon 12, making it resistant to **pathogenic caspase-6 cleavage**, which can generate toxic N-terminal fragments of huntingtin implicated in disease pathology[1][4][6][10][11]. QRX-704 acts at the RNA level to shift splicing towards the protective Δ12 isoform, which retains the essential functions of wild-type HTT but resists proteolytic fragmentation believed to drive Huntington's disease progression. In preclinical models, intracerebroventricular administration of QRX-704 led to: - Effective activation of HTT Δ12 splicing. - Significant reduction in toxic N-terminal huntingtin fragments and pathogenic aggregates. - Increased dendritic spine density in relevant brain regions. - A long tissue half-life and generally predictable pharmacokinetics. No overt toxicity, behavioral adverse effects, or astrogliosis were noted in treated animals[1][4][6][10]. QRX-704 is developed by **ProQR Therapeutics**[1][5][8][12].