eBook: Cell and Gene Therapy - 16

Generation of Cell Lines Capable
of Producing High-titer Viral
Stocks for Use in Vaccine
Manufacture and Gene Therapy
Newly created cell lines provide an efficient method for companies
to increase production while reducing costs.
Elizabeth Turner-Gillies, PhD; Brian Shapiro, PhD; and Fang Tian, PhD
Abstract
Antiviral vaccines are essential for preventing epidemic
disease; however, the production of these
therapeutics is often limited by low-yielding
manufacturing processes. Similarly, the development
of gene therapies is constrained during the
large-scale production of viral vectors, such as adeno-associated
virus (AAV) delivery platforms for
gene transfer.
To speed the pace of these various areas of bioproduction,
ATCC addressed the need for efficient
viral replication by optimizing three cell lines commonly
used in virus manufacturing. Here, we used
CRISPR/Cas9 gene-editing technology to develop
STAT1 and BAX knockout cell lines capable of producing
high-titer viral stocks. These newly created
cell lines can produce model clinical viruses and
adeno-associated viruses at titers much higher
than the parental cell lines, providing an efficient
method for biopharmaceutical companies to increase
production while reducing associated costs.
Introduction
The manufacture of antiviral vaccines using mammalian
cell systems requires the production of
large quantities of viral particles in a scaled-up
tissue culture system. A handful of historical cell
lines like Vero (African green monkey kidney) and
MDCK (canine kidney) are approved by the FDA
for the production of many viral vaccines. However,
other than clone selection and cell culture
media adaption, relatively little has been done to
improve the inherent viral production capacity
of these cell lines. Additionally, there has been a
resurgence in gene therapy, driven by the development
of safe and easy-to-use AAV vectors. As
in the process of manufacturing vaccines against
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