HSV for Neural Circuitry Research

Overview of HSV for Neural Circuitry Research

Introduction of HSV

Herpes simplex virus (HSV) refers to herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) which belong to the human herpes virus family. As a widespread human pathogen, HSVs infect 70% of people worldwide. After initial infection, the virus particles enter the sensory neurons and travel in the retrograde direction along the axons. Following enter the neuron nucleus, the viruses would remain in a latent state. HSV-1always tends to be latent in the trigeminal ganglion, while HSV-2 tends to be lurking in the sacral ganglia.

Fig.1 Amplicon vector and amplicon plasmid structure.¹

HSV-derived Vector Design

To achieve efficient genetic material delivery in mammalian cells, viral-derived vectors have been served as the most promising tools. As a naturally epithelial-neurotropic virus, neurons are target cells for HSV-1-derived vectors and HSV-1 is suitable for the design of engineered viral vectors.

From the perspective of structure, host range, as well as immunological, amplicon vectors are particles identical to wild-type HSV-1 which contains a concatemeric form of a DNA plasmid rather than the viral genome. In this case, the viral proteins cannot be synthesized, and these vectors are fully nontoxic for the infected cells and inoculated organisms. What's more, the lack of a viral genome allows a high capacity to host foreign DNA.

Fig.2 Production of amplicon vectors by co-transfecting amplicon plasmid with helper defective herpes simplex virus type 1 (HSV-1) genomes.¹

Features of HSV for Vector Application

• Wide range of cell infection types for preclinical evaluation.
• The ability to infect both dividing and non-dividing cells.
• Most of the diseases caused by HSV is not serious.
• A large transgene capacity allows the introduction of high amounts of exogenous DNA.
• Safe replication-defective HSV-1 vectors can be designed with high titers.
• The latent state in peripheral neurons for long-term expression.
• Reduced risk of insertional mutagenesis.

Services at Creative Biolabs

Our HSV services are designed to help researchers investigate, manipulate, and study neural circuits in the brain with precision and efficiency. Our services include:

• Viral Vector Construction - We provide customized viral vectors carrying fluorescent proteins, optogenetic tools, chemogenetic tools, or other genetic elements that can be used to label, isolate, or manipulate specific neural circuits.
• Viral Vector Production - We offer high-quality viral vector production services using state-of-the-art techniques to ensure high titer and purity of viral particles.
• In vivo Viral Vector Delivery - Our team of experts can assist in designing and executing viral vector injections, stereotaxic surgeries, or other delivery methods to achieve precise and efficient gene expression in neural circuits.
• Transsynaptic Tracing - We offer transsynaptic tracing services using HSV-based viral vectors to map neural circuits and study the connectivity between different brain regions.

Whether you are investigating the neural basis of a particular neurological disorder, studying the neural circuits underlying a specific behavior, or exploring the connectivity of brain regions, our services can provide valuable tools and resources for advancing your research goals. By rendering this service and related services, we aim to accelerate research and drug discovery in neurodegenerative diseases, including but not limited to:

Published Data

Monosynaptic viral tracers are important tools for dissecting neuronal connectomes and targeting delivery of molecular sensors and effectors. Feng Xiong et al. developed a forward monosynaptic H129 amplicon tracer system based on HSV-1 strain H129. They generated three different tracers to achieve a range of experimental goals. All three tracers utilize the same adjuvant to generate H129 amplicons to promote cis-diffusion into postsynaptic neurons.

The H129 amplicon tracer system consists of tracers and adjuvants whose common viral properties allow for simultaneous single injections and high expression efficiencies. The absence of virulence genes in the H129 Amp tracers minimizes toxicity to the postsynaptic neuron, thus providing the potential for functional cis mapping and long-term tracer delivery of genetic payloads.

Fig. 3 H129 amplicon-derived anterograde monosynaptic tracer system.²

Applications of HSV in Neuroscience

• The model for demyelinating disease
• Transneuronal tracing studies
• Viral vector for gene therapy
• Research for neuro-immune interactions
• Study of health effects of chronic stress

HSV-derived vectors present great potentials for fundamental research and gene therapy of neurological diseases. Creative Biolabs is one of the well-recognized experts who are professional in applying advanced platforms for a broad range of neurosciences research. Now we provide custom HSV-derived vectors for our clients all over the world. If you are interested in our services and products, please do not hesitate to contact us for more detailed information.

FAQs

Q: What kind of genetic modifications can be achieved using your HSV services?

A: Our HSV services can deliver a wide range of genetic modifications, including gene overexpression, knockdown, and knockout. We can also introduce fluorescent proteins for visualization, optogenetic tools for controlling neural activity, and Cre-lox systems for precise genetic recombination. These modifications can be tailored to your specific research needs, providing you with powerful tools to dissect neural circuits and functions.

Q: How do you ensure the specificity of HSV targeting in neural circuits?

A: Specificity in targeting is achieved through the careful design of the viral vectors. We use cell type-specific promoters, which ensure that gene expression occurs only in the desired neuron populations. Additionally, we can incorporate retrograde and anterograde tracing capabilities to map out specific neural pathways. Combining these approaches ensures that the HSV vectors target only the intended neural circuits.

Q: How long does it typically take to receive the custom HSV vectors after placing an order?

A: The timeline for receiving custom HSV vectors typically ranges from 4 to 6 weeks, depending on the complexity of the vector design and current demand. This includes vector construction, quality control, and validation. We prioritize ensuring that the vectors meet the highest standards of quality and functionality before delivery, providing you with reliable tools for your research.

Q: How do you verify the quality and efficacy of your HSV vectors before shipping them to customers?

A: Quality and efficacy are verified through a series of rigorous tests. We perform PCR and sequencing to confirm the genetic integrity of the vectors. Additionally, we conduct functional assays, such as transduction efficiency tests in relevant cell lines, to ensure the vectors perform as expected. Each batch undergoes thorough quality control checks, and we provide a certificate of analysis with every order to guarantee the highest standards.

Scientific Resources

Comparison of Various Viral Vectors in the Central Nervous System

References

1. Baez, M.; et al. Using Herpes Simplex Virus Type 1-Based Amplicon Vectors for Neuroscience Research and Gene Therapy of Neurologic Diseases. Molecular-Genetic and Statistical Techniques for Behavioral and Neural Research. 2018, 445-477.
2. Xiong, Feng, et al. "An HSV-1-H129 amplicon tracer system for rapid and efficient monosynaptic anterograde neural circuit tracing." Nature Communications 13.1 (2022): 7645.

For Research Use Only. Not For Clinical Use.