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Rational cell design for superior adenovirus production

Researchers uncover what dictates the productivity of adenovirus vectors cell-lines

Oeiras, 06.06.2013

Adenovirus vectors have been extensively studied for gene therapy applications but not so much attention has been paid to the producing cell lines, which are empirically selected through extensive virus production screenings. Researchers from the Animal Cell Technology Unit now show that by rationally tinkering with the cells it is possible to increase the production of adenovirus vectors. The findings are published in PloS One.

Replication-defective vectors are the most common choice in gene therapy. These viruses are capable of infecting target cells and delivering the genetic material but then fail to continue the typical pathway that leads to cell lysis and death. But for manufacturing, the replication function is necessary to enable a productive virus cycle, so that function must be provided (in trans) by the cell line. Typically developing such cell lines is time demanding.

In particular, researchers evaluated the effect of expressing the E1 region in trans. This region codes for two subunits – E1A and E1B – with different effects in virus production: while high levels of E1A are proportional to virus amplification, high E1B expression prolonged cell viability, contributing differently to the global viral titer. These findings highlight the importance of considering the cell’s ability to express high levels of E1A and E1B to increase both the adenovirus yields and quality.

Original Article

PLoS One. 2013;8(4)

Impact of E1 and Cre on Adenovirus Vector Amplification: Developing MDCK CAV-2-E1 and E1-Cre Transcomplementing Cell Lines

Paulo Fernandes, Virgínia M. Santiago, Ana F. Rodrigues, Hélio Tomás, Eric J. Kremer, Paula M. Alves and Ana S. Coroadinha

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