Alzheimer disease

In the past decades, the adeno-associated virus (AAV) has been developed as a promising nonpathogenic vector of gene therapy to treat neurodegenerative diseases in the central nervous system (CNS). With expertise in AAV and years of experience, Creative Biolabs offers a wide range of AAV vector design service to suit your basic research and gene therapy needs.

Introduction of Alzheimer Disease

Alzheimer disease (AD) is an age-related neurodegenerative disorder involving progressive degeneration in regions of the brain that are important for memory and cognition. The neuropathological hallmarks of AD include extracellular accumulation and aggregation of the amyloid β-peptide (Aβ) into plaques and intracellular accumulation and aggregation of hyperphosphorylated tau protein, forming neurofibrillary tangles (NFTs). However, the mechanisms underlying these neuropathological changes remain unclear. The majority of AD cases are sporadic in nature but approximately 5 % are caused by a specific genetic polymorphism in the amyloid precursor protein gene (APP) or presenilin genes (PS1 or PS2) that make up part of the APP-cleaving complex. To date, there are no treatments can stop the progression of the disease. Recently, several gene therapy strategies have been evaluated, targeting different pathways involved in AD physiopathology, and some have gotten encouraging results via gene replacement or gene correction.

AAV-based Gene Therapy for AD

Gene therapy provides the potential for transformative therapies to delay or stop further progression of AD in affected patients. The AAV vector has been the first choice in recent clinical trials for AD due to its safety and efficiency in mediating gene transfer to the CNS. AAV-mediated gene therapy allows novel treatments of AD, particularly with recombinant AAV (rAAV). Strategies to reduce the amyloid accumulation by increasing amyloid-degrading proteases, such as neprilysin (NEP) and endothelin-converting enzyme (ECE), or by delivering anti-Aβ monoclonal antibody (mAb) into the corticohippocampal regions of AD mice using AAV vectors, are shown to decrease plaques and Aβ in the cortex and hippocampus of AD mice models with no sign of neurotoxicity.

For instance, cDNAs encoding heavy and light chains of anti-Aβ mAb were subcloned into AAV vectors and significantly reduced Aβ levels, which supports the use of AAV vector encoding Aβ mAb for the prevention and treatment of AD. In addition, the nonamyloidogenic pathway of APP metabolism prevents the production of amyloid toxic forms and enables the release of soluble APPsɑ, which is thought to be responsible for the important physiological functions of APP. Increasing the physiological APP pathway is thus an interesting strategy to treat AD, and APPsɑ overexpression by AAV could alleviate AD-related symptoms.

Services

AAV vectors are the ideal tools for inserting genes into a broad range of cell types with high efficiency and enhanced safety. Eleven serotypes of AAV have been identified to date, with the best characterized and most commonly used being AAV2. Creative Biolabs offers manufacture service for a range of AAV serotypes in combination with tissue-specific promoters to further increase gene expression precision in CNS. We provide high-quality AAV vector design services to meet the gene therapy needs of AD. The success of AAV for gene therapy is also dependent on vector quality and titer. Alongside our AAV vector design service for gene therapy, we also provide virus amplification, purification, titration, and toxicity and safety determination.

Advantages

• High titers. The titer of purified AAV particles can be up to 10¹⁴ GC/ml.
• High adaptability. Almost all serotypes are available.
• Versatile. Can be used in a broad range of host cell types.
• Low toxicity. Does not integrate into the host genome.
• Low immunogenicity. Minimal host immune response.
• Safe. Not associated with any human disease.

When choosing our custom AAV service, Creative Biolabs's technical experts will assist you to identify the optimal setting for your specific application and design AAV vectors exactly to your specification. For more details, please contact us and we will be happy to assist you.