Wednesday, June 18, 2014

Removing Bottlenecks in Cell Line Engineering

There are several known bottlenecks in generating mammalian cell clones to produce therapeutic proteins.  Dr. Nic Mermod, Director of the Institute of Biotechnology at the University of Lausanne, cites biological issues, such as transcription levels, as well as process issues, including the cloning and maintenance of many cells, as causes of these bottlenecks.  Dr. Mermod, who will be speaking at this year’s Cell Line Development & Engineering conference, has several ideas on removing said bottlenecks.  Some thoughts from this leader in the field:

What are the current approaches when removing such bottlenecks?

Dr. Mermod: The first bottleneck is transcription of the transgene. We have been working on the element called MAR, which can remove some of the negative effects of integration of the transgene into a non-favorable genetic environment. And other people are also working on other elements. That – for the MAR elements –allows to, pretty much, dampen some silencing effects and also to prevent oscillation of transcription, whereby you get the transgene active at all times within all cells.

So, that’s one way to alleviate low levels of transcription. Another way, of course, is to basically increase transgene copy number. That is to work on the recombination mechanism to allow your CHO cells to more efficiently integrate transgene, if you want to further boost the level up.

And then for basic protein metabolism and secretion, there are efforts by a number of laboratories to perform genomic engineering of the CHO cell. For instance, we have reengineered the human secretion machinery in CHO-M cells which allows to increase protein secretion of easy or difficult to express proteins; both of them. So, that’s basically the current approach that we and others are taking.

To check out our full interview with Dr. Nic Mermod, download the Cell Line Development and Engineering brochure.

Cell Line Challenges BottleneckWe’ll have more from Nic at this year’s Cell Line Development & Engineering conference.  Join us September 8-10 in Berkeley, CA.  Save 20%* off the standard rate as a reader of this blog when you register here and use discount code XB14189BLOG.   

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