Huntington's Disease (HD)
Huntington's disease (HD), a disease with abnormal gene amplification, threatens the health of many people in Europe and the United States. Since there is no universal treatment method to treat this disease, delay its onset or slow down the progress of patient decline, we need targeted gene correction to change the health status of patients. With Creative Biolabs' adeno-associated virus (AAV) vector design platform, we can design recombinant AAV gene vectors for the treatment of Huntington's disease, targeting the brain and other pathogenesis organs. AAV gene vector can be used to silence the Huntington gene or other gene therapy programs you have planned.
Introduction of Huntington's Disease
HD is a rare, fatal neurodegenerative genetic disease that causes young people's behavioral and cognitive declines, resulting in physical and mental deterioration. The genetic cause of HD is that the pathogenic amplification of the CAG tract in exon 1 of the Huntington Gene (HTT) exceeds 35 replicates, with longer repeat lengths leading to the earlier onset and increased disease severity. HD in adults is usually manifested in a wide range of sports, cognitive and mental illnesses around the age of 40. The single-gene nature of HD and the development of predictive tests for the genetic diagnosis of HD allow for the reliable identification of gene vectors before the onset of symptoms. Thus, treatment of HD can be initiated in the early stage of the disease, when it may prevent or even reverse neuronal dysfunction. Currently, the treatment of HD patients is mainly based on the use of appropriate small-molecule drugs according to the symptoms of patients. The lack of research on the pathological mechanism of this disease leads to a high failure rate of new drug development.
Reducing the level of toxic mHTT protein is a very promising approach in HD therapy. However, the reduction of the expression level of wild-type mHTT has an effect on some important organs, and further research is needed on the degree of HTT reduction that humans can tolerate. Allelic selective silencing of mutant HTT alleles is a more direct and potentially safer treatment for HD. Allele selectivity can be achieved by targeting the extended CAG region of the mutant allele or by targeting other HTT polymorphisms, such as single nucleotide polymorphisms (SNPs) and linkage disequilibrium with CAG amplification, nucleotide insertions and deletions (INDEL).
Figure 1. Pathogenesis of HD.
rAAV Gene Therapy for HD
RNAi-based strategies for HTT silencing have great potential as therapies for HD and are amenable to nonselective and allele-selective approaches. Currently, delivery of RNAi agents using AAV and lentiviral vectors has been used to achieve long-term HTT reduction in the CNS. Unlike lentiviral vectors that stably integrate into the host cell genome, AAV vectors remain predominantly episomal after transduction, which reduces the likelihood of random insertion mutagenesis. In addition, AAV is able to efficiently transduce non-dividing cells, which will provide the sustained expression of the silencing agent after a single administration. Furthermore, AAV9-encoded miRNAs that target systemically delivered mHTT by intravenous injection substantially inhibited mHTT levels in the peripheral and central nervous system and reduced brain atrophy in the HD mouse model.
Creative Biolabs inhibits the production of mutant mHTT proteins by constructing a safe and effective gene therapy AAV vector. Our vectors are highly targeted, allowing microRNAs to be delivered directly to the brain and non-selectively knock out the Huntingtin gene. This is a highly innovative and promising approach to treating HD.
If you have any questions about our vector design service, you can contact us by email or send us an inquiry to find a complete solution.
