Organic Vectors | Esco VacciXcell

Organic Vector: The Pillar of Gene Therapy 

An organic viral vector is a biological tool used to deliver genetic material into cells. It is derived from a virus that has been modified to remove its harmful properties and replace them with therapeutic genes. The modified virus can then be used as a carrier or vector to deliver the therapeutic genes into target cells.

Organic viral vectors have been extensively used in gene therapy to treat a variety of diseases, such as cancer, genetic disorders, and viral infections. They have several advantages over non-viral vectors, including high efficiency, low toxicity, and the ability to integrate the therapeutic genes into the genome of the host cell, which allows for long-term expression.

In gene therapy, organic viral vectors are used to deliver functional copies of genes to replace or correct mutations that cause genetic diseases. These viral vectors are designed to be non-pathogenic and safe for human use, and they can be engineered to target specific tissues or cell types, which increases their efficacy.

Types of Organic Viral Vectors

There are several types of Organic Viral Vectors.These include retroviruses, adenoviruses, adeno-associated viruses (AAVs), and lentiviruses. Each of these viruses has unique properties that make them suitable for specific applications in gene therapy.

organic vector

Adenovirus: Adenoviruses are a family of viruses that can cause respiratory illness, but they have also been modified for use as viral vectors in gene therapy. Adenoviral vectors can deliver genes to a wide range of cells and tissues, and they are known for their high efficiency of gene transfer. They can also accommodate large genes and can be produced in large quantities. Adenoviral vectors can cause an adaptive immune response. When the adenoviral vector is introduced into the body, it is recognized as a foreign invader by the immune system. This triggers the activation of immune cells such as T cells and B cells, which can mount a targeted attack against the vector. This immune response can result in the production of antibodies against the adenoviral vector, which can limit the effectiveness of the vector in the long term. Additionally, repeated administration of adenoviral vectors can lead to a stronger immune response and the development of immunity to the vector itself, further limiting its effectiveness.

Lentivirus: Lentiviruses are a type of retrovirus that can integrate their genetic material into the host cell's genome. Lentiviral vectors are commonly used in gene therapy because they can deliver genes to dividing and non-dividing cells which makes them suitable for targeting tissues that are difficult to reach with other vectors. They also have a large cargo capacity and can accommodate larger genes than other vectors. However, like all retroviruses, lentiviral vectors have the potential to cause mutagenesis and insertional oncogenesis, which is a safety concern.

adeno-associated virus

Adeno-associated virus (AAV): Adeno-associated viruses are small, non-pathogenic viruses that have become popular vectors for gene therapy because they have a low immunogenicity and are generally safe to use. AAV vectors can deliver genes to both dividing and non-dividing cells, and they are designed to target specific types of cells or tissues. They also have a low integration rate which can reduce the risk of insertional mutagenesis.

However, they can still elicit an immune response, which can be classified into two types: innate and adaptive immune responses.

  1. The innate immune response is the immediate, non-specific response that occurs when the AAV vector is introduced into the body. This response is characterized by the activation of immune cells such as macrophages, dendritic cells, and natural killer cells, which recognize the AAV vector as a foreign invader and attempt to clear it from the body.
  2. The adaptive immune response is a more targeted and specific response that occurs when the immune system recognizes the AAV vector as foreign and mounts an attack against it. This response can result in the production of antibodies against the AAV vector, which can limit the effectiveness of the vector in the long term.
Herpes simplex virus

Herpes simplex virus (HSV) vectors: HSV is a DNA virus that can infect both dividing and non-dividing cells. HSV vectors are effective at delivering genes to neurons, and they can be used to treat neurological disorders.

Vaccinia virus vectors: Vaccinia virus is a DNA virus that can infect both dividing and non-dividing cells. Vaccinia virus vectors are effective at delivering genes to a wide variety of cell types, and they can be used to treat cancer and infectious diseases.

Measles virus vectors: Measles virus is an RNA virus that can infect both dividing and non-dividing cells. Measles virus vectors are effective at delivering genes to immune cells, and they can be used to treat cancer and infectious diseases.

Each type of viral vector has its own advantages and limitations, and the choice of vector depends on the specific application and the type of cells or tissues being targeted.

 Advantages of Organic Viral Vectors

Organic viral vectors have several advantages as gene delivery vehicles in gene therapy, including:

  1. High efficiency: Organic viral vectors can efficiently deliver genes to target cells, resulting in high levels of gene expression. This is especially important for diseases that require high levels of gene expression to achieve therapeutic effects.
  2. Targeted delivery: Organic viral vectors can be engineered to target specific cell types or tissues, which reduces the risk of off-target effects and increases the specificity of gene therapy.
  3. Ability to integrate into host genome: Some types of organic viral vectors, such as retroviral vectors, can integrate their genetic material into the host cell's genome. This allows for stable and long-term gene expression.
  4. Low immunogenicity: Organic viral vectors are generally well-tolerated by the immune system, which reduces the risk of immune responses that can limit the effectiveness of gene therapy.
  5. Large cargo capacity: Organic viral vectors can carry relatively large genetic payloads, which allows for the delivery of multiple genes or larger genes that cannot be delivered by non-viral methods.
  6. Broad range of applications: Organic viral vectors can be used to treat a wide variety of diseases, including genetic disorders, cancer, and infectious diseases.

These advantages make organic viral vectors a promising tool for gene therapy, and researchers continue to explore ways to improve their safety, specificity, and efficacy.

VIRAL VECTOR PRODUCTION IN TIDE MOTION SYSTEM

viral vector production in Tide Motion Systems

Viral vector production in Esco VacciXcell’s Tide motion technology has the ability to produce viral vectors using the proprietary gentle upward and downward motion of the culture medium to enhance the growth and productivity of cells used in the production process.

Tide Motion bioreactors are designed to mimic the natural environment of cells, providing a more gentle and efficient means of culturing them compared to traditional static systems. This can lead to higher cell densities and increased productivity, making them a popular choice for viral vector production.

To produce viral vectors in a tide motion system, cells are typically grown in a culture vessel that is mounted on a rocking platform. This provides the cells with the necessary oxygen and nutrients they need to grow and produce viral vectors.

The specific process for producing viral vectors in a Tide motion system can vary depending on the type of vector being produced and the specific bioreactor being used. These are the general steps typically involved in the process.

  1. Culturing the cells used to produce the viral vector in the Tide motion system.
  2. Transfecting the cells with the viral vector construct.
  3. Allowing the cells to produce the viral vector.
  4. Harvesting and purifying the viral vector from the culture medium.

Overall, the use of Tide motion bioreactors in viral vector production can help increase productivity, reduce production costs, and improve the quality and consistency of the final product.

References:

  • Hirsch, M. L., et al. "Adeno-associated virus vectors as a tool for large-scale manufacture of recombinant adeno-associated virus vectors." Journal of Visualized Experiments, vol. 97, e52452 (2015). 
  • Kim, Y. J., et al. "Non-viral, targeted gene editing in tomato plants using gemini virus replicon-based vectors." Plant Biotechnology Journal, vol. 18, no. 9, pp. 1843-1853 (2020). 
  • Kurosaki, T., et al. "Organic non-viral gene delivery: a review of the current state-of-the-art." Drug Discovery Today, vol. 24, no. 2, pp. 373-380 (2019).
  • Lim, K. I., et al. "Optimization of high-titer lentiviral vector production using polyethylenimine-mediated transfection." Gene Therapy, vol. 20, no. 3, pp. 246-254 (2013). 
  • Martínez-Navarrete, G., et al. "Adeno-associated virus vectors as a tool for gene transfer in the central nervous system." Journal of Physiology and Biochemistry, vol. 71, no. 4, pp. 547-556 (2015).