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.
We’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.
Sign up for updates
Check us out on LinkedIn
Follow us on Twitter
Like us on Facebook
*New
registrants only
|
Share this article with your social network, just click below to share now!
|
|
|
No comments :
Post a Comment