AAV for Neural Circuitry Research

Introduction of AAV

Adeno-associated viruses (AAVs) are small viruses belong to the genus Dependoparvovirus.With a length of 4.7 kb, the AAV genome is composed of two open reading frames (ORFs), Cap and Rep, which are flanked by inverted terminal repeats (ITRs). Till now, 11 natural serotypes of AAVs have been identified. AAVs are nonenveloped viruses, the gene expression and replication can be activated when the helper viruses are present. Compared to other vectors, the frequency of random integration into the genome of the host cell is much lower. In addition, removing Rep and Cap can further prevent the integrative capacity.

Fig.1 Novel adeno-associated virus (AAV) viral vector-mediated non-trans-synaptic retrograde tracing and trans-blood-brain barrier labeling. (Wang, 2018)

AAV-Based Gene Therapies in Neuroscience

Due to the lack of replication ability and extremely low immunogenicity, AAV has been widely used in neuroscience and gene therapy. To date, there are more than 110 AAV-related gene therapies for clinical trials in the world. The disease indications include but are not limited to:

• Parkinson's disease
• Alzheimer's disease
• Spinal muscular atrophy
• Amyotrophic lateral sclerosis
• Temporal lobe epilepsy
• Charcot-Marie-Tooth disease type 1A

Applications of AAV in Neuroscience

In general, we use the brain stereotactic injection technique to deliver viral vectors to specific brain regions for the expression of specific genes and fluorescence. However, it is not suitable for extensive labeling and gene expression in multiple brain regions because of the limited virus infection efficiency. In this case, the injection of AAV can solve this problem and further improve a variety of research and gene therapy methods.

It is well-known that traditional AAV vectors cannot cross the synapses. In this case, anterograde tracing and retrograde tracing are essential to characterize neuronal networks. Among them, anterograde tracing focuses on labeling known downstream brain regions, while retrograde tracing focuses on upstream brain regions. Compared with fluorescent dyes, viral vectors have the capabilities of retrograde tracking and gene carry. The established rAAV2-retro serotype vector can be absorbed in the axon and retrograde to the nucleus for the expression of fluorescent protein along the cytoskeleton.

Fig.2 Transcriptional targeting of neuronal populations. (Haggerty, 2020)

Features of AAV

• High gene delivery ability
• Low immunogenicity
• Capsid protein diversity
• High infection efficiency

Creative Biolabs is one of the well-recognized experts who are professional in applying advanced platforms for a broad range of neurosciences research. We are pleased to use our extensive experience to offer the best service and the most qualified products to satisfy each demand from our customers. If you are interested in our services and products, please do not hesitate to contact us for more detailed information.

References

1. Wang, Y.; et al. Viral vectors as a novel tool for clinical and neuropsychiatric research applications. General psychiatry. 2018, 31(2).
2. Haggerty, D.; et al. Adeno-associated viral vectors in neuroscience research. Molecular Therapy-Methods & Clinical Development. 2020, 17: 69-82.

For Research Use Only. Not For Clinical Use.