Viral Vectors We Support

Viral Vector: Lentivirus

Lentiviruses (LVs) are virulent agents that infect host cells via the genomic incorporation of viral cDNA. While many naturally occurring LVs are responsible for deadly diseases, their highly evolved infection efficiency has been leveraged in biotechnology, such as vectors for genome editing in mammalian cell lines and animal models. Engineered LVs have been used to knock out, upregulate, and insert new genes into the genome of mammalian cells and animal models to generate therapeutics and model diseases.

The Approach

Compared to other viral vectors, LVs offer the unique advantage of being able to infect both mitotic and post-mitotic cells. This is particularly useful for cell types with low division rates or no division at all, such as neurons. For genetically-modified cell therapies, the gene modification process involves the addition of a viral vector to the culture vessel. For CAR-T, the vector is typically an integrating viral vector, such as lentivirus.

The Challenge

In recent years, laboratories have been seeking ways to reduce the cost of manufacturing CAR-T products – and in particular the LVs that transduce them – to increase the accessibility of the CAR-T treatment. Traditionally, adherent HEK293T cells are transiently transfected with second or third generation vectors to generate LV particles. Although this approach serves the need for preclinical research labs, adherent cells pose inherent difficulties when scaling up to produce GMP grade vectors.

The Theragent viral vector lab is continuously
exploring innovative methods for enhancing lentiviral
vector yield and target cell infectivity.

LVs are used in gene therapies to alter genetic information pertaining to disease states. Cells, such as hematopoietic stem cells (HSCs) or T cells harvested from donors for allogeneic transplant or patients for autologous transplant, are infected with LVs containing genes of interest to make the cell-based therapy more robust. Three LV therapies are FDA approved, with hundreds more in clinical trials.

Historically, LVs have been grown in small-scale productions involving adherent cultures and serum-based media that resulted in low yield and immunogenicity risks. With optimized suspension cultures in serum-free media, LVs can be produced at a commercial scale that is ready
for clinical use.

To that end, the Theragent viral vector lab is continuously exploring innovative methods for enhancing lentiviral vector yield and target cell infectivity. Reach out to our LV experts to learn more about our new viral production cell lines using serum-free media can increase lentiviral vector titers.

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