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 for use as vectors to conduct genome editing in mammalian cell lines and animal models. Engineered LVs have been used as a major delivery vehicle to carry gene editing tools to knock-out or knock-in genes or regulate gene expression to generate therapeutics. In these gene-modified cell therapies, LVs are used to integrate genetic information to cells that are to be injected back into patients post modification. Multiple such LV based gene-modified cell therapies are now FDA approved, and hundreds more are in clinical trials.

The Approach

Compared to other viral vectors, LVs offer the unique advantage of being able to infect both mitotic and post-mitotic cells. This provides a wide range of possible applications, including Neurons or beta-islet cells which have a low division rate or even do not divide at all. For genetically-modified cell therapies, LVs are used to deliver the gene of interest and have it integrate into the genome of the targeted cell types. This insertion allows the targeted cells to express functional protein, or RNA, for therapeutic purposes.

The Challenge

In recent years, CAR-T therapies have become one of the most promising cancer therapeutic options and a large number of products are under development. CAR-T therapy is still a new and expensive treatment, and to increase accessibility of this new therapeutic modality, laboratories are seeking ways to reduce the cost of manufacturing CAR-T products.  Since the manufacture of LVs is one of the major cost components, improvement in  the production efficiency and reduction in the production cost of LV is and will continue to be a major focus within the field.

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

Traditionally, adherent HEK293T cells have been used to generate LV particles. Although this approach serves the need for preclinical research labs, adherent cells pose inherent difficulties, including the operational space requirements, culture volume limitations, and culture media supply. Meanwhile, adherent LV production methods have been performed with the serum-based media that result in low yield and immunogenicity risks.

All of these items create obstacles when scaling up GMP vector production.

To address the issues, the Theragent viral vector lab is continuously exploring innovative methods. Current explorations in development include an optimized high-yield viral production procedure, suspension culture cell lines derived from and grown in serum-free media, and genetically modified HEK cell lines for increasing both viral production efficiency and gene insertion capacity of the vector. Through these ongoing improvements, Theragent‘s LV production can be performed in a more economical manner compared to the current commercial process.

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