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Derived from adeno-associated viruses (AAV), AAV vectors dominate clinical trials for CNS diseases due to their efficient broad-cell infection and strong neuronal tropism. AAV's low integration rate enhances safety. As an AAV technology leader, Creative Biogene proudly offers AAV viral vectors as vital research tools for investigating Parkinson's disease mechanisms. Our Parkinson's disease tools include vectors for knocking down wild-type and mutant α-synuclein (αSyn) and an A53T α-synuclein viral vector associated with familial Parkinson's disease. With an excellent safety profile, our AAV tools ensure efficient transduction and enduring neuron expression, available immediately for in vitro or in vivo research.
The αSyn-targeting AAV vectors incorporate transgenes to either overexpress wildtype or A53T mutant αSyn or express shRNAs to suppress αSyn expression. Introducing these modulation tools into dopaminergic neurons using AAV capsids with neuronal tropism like PHP.B or PHP.eB can establish cellular models that mimic Parkinson's disease pathology. The principle involves stereotactic injection into substantia nigra regions enabling the transduction of susceptible neuron populations. The resulting overexpression or knockdown of αSyn allows new insights into downstream impacts on neuronal viability, motor deficits, and neurodegeneration. Testing novel therapeutics in the AAV gene delivery models provides an accurate context reflecting endogenous disease. The Creative Biogene AAV-αSyn vectors enable unique Parkinson's disease models to elucidate mechanisms and evaluate potential genetic and pharmacologic treatments. Our products can assist you in the following tasks:
Case Study 1
Lewy body dementias exhibit the accumulation of protein aggregates, specifically synuclein (α-syn), forming structures called Lewy bodies and Lewy neurites. These aggregates are present not only in the brainstem but also in cortical regions. The researchers used AAVs to overexpress α-syn in the medial prefrontal cortex of mice to model early Lewy body dementia pathology. After 10 weeks, Golgi-Cox staining showed increased dendritic spine density in layer 5 pyramidal neurons compared to the control virus. Immunostaining revealed human α-syn expression in presynaptic terminals across the region, with some phosphorylated α-syn limited to somas and nuclei at highest expression sites. These results demonstrate cortical α-syn overexpression may initially alter connectivity, relevant to early disease stages.
Figure 1. Animals were randomized to injection with either vector coding for expression of a control protein, mCherry: AAV2/6-CAG-mCherry-WPRE or vector coding for human, wild-type alphasynuclein: AAV2/6-CAG-hSNCA-WPRE. After 10 weeks, Golgi-Cox staining and analysis assessed dendritic spines. (Wagner L, et al., 2020)
Case Study 2
The second most prevalent movement disorder, Parkinson's disease (PD), is marked by the degeneration of up to 80% of dopamine (DA) neurons and the buildup of α-synuclein (α-syn) deposits known as Lewy bodies. The researchers injected AAV-α-syn into the substantia nigra of T cell deficient or competent rats. T cell competent rats developed paw bias and dopamine neuron loss with microglial activation and CD4/CD8 T cell infiltration. In contrast, T cell-deficient rats injected with AAV-α-syn showed no behavioral deficits, microglial activation, or neuron loss compared to controls. The results demonstrate that T cells contribute to neurodegeneration in this AAV Parkinson's model, entering after microglial activation and correlating with peak dopamine neuron loss.
Figure 2. AAV-α-syn increased Iba1+ microglia in both rat strains, but only competent rats showed MHCII+ activation and recruitment, lacking in T cell deficient rats. (Subbarayan M S, et al., 2020)
Q: How is the AAV vector engineered to carry genes associated with Parkinson's disease, such as SNCA A53T?
A: The AAV vector is meticulously designed using synthetic biology techniques. Specific regulatory elements, including neuron-specific promoters like Syn, are employed. These elements ensure targeted and efficient transgene expression associated with Parkinson's disease.
Q: Can you provide insights into the transduction efficiency of AAV vectors in neuronal cells relevant to Parkinson's disease?
A: Transduction efficiency is optimized through the careful selection of AAV capsid serotypes. Our vectors utilize serotypes known for their superior transduction capabilities in neural tissues.
Q: In the context of AAV-mediated gene delivery, how are functional studies conducted to assess the impact on neuronal activity and Parkinson's disease-related pathways?
A: Functional studies involve the integration of biosensors or reporters into AAV constructs. This enables real-time monitoring of neuronal dynamics, facilitating a detailed assessment of the impact on Parkinson's disease-related pathways.
Q: What strategies are employed to ensure long-term and stable expression of transgenes delivered by AAV vectors in the context of Parkinson's disease models?
A: Strategies include utilizing AAV constructs with episomal genomes. This ensures persistent and stable transgene expression, addressing the need for extended studies in Parkinson's disease models.
| Cat.No. | Product Name | Price |
|---|---|---|
| AAP0001 | AAV1-CBA-Human-SNCA-A53T | Inquiry |
| AAP0002 | AAV1-CAG-GFP/Scrambled-miRNA | Inquiry |
| AAP0003 | AAV1-CBA-Null | Inquiry |
| AAP0004 | AAV1-CAG-GFP/Mouse-SNCA-miRNA | Inquiry |
| AAP0005 | AAV1-CAG-GFP/Human-SNCA-miRNA | Inquiry |
| AAP0006 | AAV1-CMV-human-A53T-alpha-synuclein-WPRE-BGH-polyA | Inquiry |
| AAP0007 | AAV1-CAG-Scrambled-Control-3xSCRmiR/GFP-WPRE-BGH-polyA | Inquiry |
| AAP0008 | AAV1-CMV-Null-WPRE-BGH-polyA | Inquiry |
| AAP0009 | AAV1-CAG-Mouse-SNCA-3xmiR/GFP-WPRE-BGH-polyA | Inquiry |
| AAP0010 | AAV1-CAG-Human-SNCA-3xmiR/GFP-WPRE-BGH-polyA | Inquiry |
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