Viral Transduction Enhancers

What is Viral Transduction?

Viral transduction is a technique that utilizes viruses or viral particles as vectors to deliver genetic material into a cell. The viral vectors are generated in a packaging cell line, commonly HEK293 cells. A plasmid containing the genetic material to be transferred is inserted into the packaging cell line, along with plasmids that code viral genes for reverse transcriptase, integrase and the viral capsid. The packaging cell line produces viral vectors that replicate within cells, which are then harvested and used to transduce target cells.

Viral Transduction Enhancers are small molecules that are used to improve the efficiency of the viral transduction process.

Small Molecule Viral Transduction Enhancers

One drawback in the use of viral gene delivery is that transduction efficiency is typically low, however it has been shown that small molecules can enhance viral transduction. This allows for the use of less viral vector and may also enable the transduction of cell types that are difficult to infect. Small molecules target a variety of cellular processes to facilitate viral gene expression, including gene transcription, cell entry or DNA replication. Some compounds act by enhancing the viral cell entry, by triggering fusion or reducing the repulsion between vector and target cell, while others act intracellularly, following cell entry. However, the mechanisms by which many of these compounds enhance viral transduction remain unclear. It has been found that combining transduction enhancers has an additive effect.

A range of different types of small molecules have been shown to improve viral transduction efficiency, including DNA damage inducers (e.g. Etoposide, Cat. No. 1226), proteasome inhibitors (e.g. MG 132, Cat. No. 1748) and immunosuppressants (e.g. Dexamethasone, Cat. No. 1126). In addition, many of these compounds are FDA-approved medicines, which is beneficial in clinical application of the technique. For example, Prostaglandin E₂ (Cat. No. 2296), a compound used in labor induction, improves lentiviral transduction and increases viral vector copy numbers, resulting in increased transgene expression in CD34⁺ hematopoietic stem and progenitor cells (see figure 1).

Using Small Molecules to Enhance Viral Transduction

Figure 1: Schematic highlighting the use of small molecules to enhance viral transduction in cell and gene therapy. Top: Rosuvastatin was used to improve efficiency of lentiviral transduction in NK cells to generate CAR-NK cells for adoptive cell immunotherapy; from Gong et al (2020) Rosuvastatin enhances VSV-G lentiviral transduction of NK cells via upregulation of the low-density lipoprotein receptor. Mol.Ther.Methods Clin.Dev. 17 634. Middle: Prostaglandin E₂ was used to enhance lentiviral introduction of genes into CD34⁺ cells for gene therapy; from Heffner et al (2018) Prostaglandin E₂ increases lentiviral vector transduction efficiency of adult human hematopoietic stem and progenitor cells. Mol.Ther. 26 320. Bottom: Retroviral transduction of T cells for generation of anti-CD19 CAR T-cells was enhanced using AKTi-1/2; from Klebanoff et al (2017) Inhibition of AKT signaling uncouples T cell differentiation from expansion for receptor-engineered adoptive immunotherapy. JCI Insight 2 e95103. CAR/TCR, chimeric antigen receptor T-cell receptor; HSC, hematopoietic stem cell; NK, natural killer cell; VSV-G, vesicular stomatitis virus G.

What is Viral Transduction Used For?

Viral transduction is widley utilized by researchers for a range of processes, including but not limited to transgene expression, gene silencing, site-directed gene editing, generation of transgenic animals, expression of fluorescent proteins for imaging, reprogramming of somatic cells to pluripotent stem cells and stem cell differentiation.

Viral gene delivery also has potential in a therapeutic setting in the form of gene therapy. It may be used to introduce new genetic material to treat diseases associated with faulty genes or to treat cancer, for example CAR T-cell therapy in which a patient's blood cells are virally transduced ex vivo to enable them to bind and kill tumor cells.

Commonly Used Viral Vectors

There are three main types of virus used for viral transduction; retroviruses, lentiviruses and adeno-associated viruses. Retroviruses are stable and replication-defective, meaning they don't contain sequences required by the virus to make proteins for viral replication and infection. However, retroviral transduction can only be used in cells that are actively dividing and is unsuitable for use with cells that are post-mitotic, such as neurons. Lentiviruses are a subtype of retroviruses that can transfect non-dividing cells. Following introduction of genetic material into the host cell genome via lentiviral transduction, the viral vector remains in the cell, being passed to its progeny when the cell divides. Adeno-associated viruses also incorporate into the host cell genome and can infect both dividing and non-dividing cells.

Literature for Viral Transduction Enhancers

Tocris offers the following scientific literature for Viral Transduction Enhancers to showcase our products. We invite you to request* your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.

Stem Cell Research Product Guide

This product guide provides a background to the use of small molecules in stem cell research and lists over 200 products for use in:

• Self-renewal and Maintenance
• Differentiation
• Reprogramming
• Organoid Generation
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