PMID- 26523469
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20161230
IS  - 1097-0290 (Electronic)
IS  - 0006-3592 (Linking)
VI  - 113
IP  - 5
DP  - 2016 May
TI  - Improving expression of recombinant human IGF-1 using IGF-1R knockout CHO cell 
      lines.
PG  - 1094-101
LID - 10.1002/bit.25877 [doi]
AB  - Chinese Hamster Ovary (CHO) cells are widely used for the large-scale production 
      of recombinant biopharmaceuticals. However, attempts to express IGF-1 (a mutated 
      human Insulin-like growth factor 1 Ea peptide (hIGF-1Ea mut)) in CHO cells 
      resulted in poor cell growth and low productivity (0.1-0.2 g/L). Human IGF-1 
      variants negatively impacted CHO cell growth via the IGF-1 receptor (IGF-1R). 
      Therefore knockout (KO) of the IGF-1R gene in two different CHO cell lines as 
      well as knockdown (KD) of IGF-1R in one CHO cell line were performed. These cell 
      line engineering approaches decreased significantly the hIGF-1 mediated cell 
      growth inhibition and increased productivity of both KO CHO cell lines as well as 
      of the KD CHO cell line. A productivity increase of 10-fold at pool level and 
      sevenfold at clone level was achieved, resulting in a titer of 1.3 g/L. This data 
      illustrate that cell line engineering approaches are powerful tools to improve 
      the yields of recombinant proteins which are difficult to produce in CHO cells.
CI  - (c) 2015 Wiley Periodicals, Inc.
FAU - Romand, Sandrine
AU  - Romand S
AD  - Integrated Biologics Profiling, Novartis Pharma, Klybeckstrasse 141, Basel, 4057, 
      Switzerland.
FAU - Jostock, Thomas
AU  - Jostock T
AD  - Integrated Biologics Profiling, Novartis Pharma, Klybeckstrasse 141, Basel, 4057, 
      Switzerland.
FAU - Fornaro, Mara
AU  - Fornaro M
AD  - Musculoskeletal Diseases, Novartis Institute for BioMedical Research, Basel, 
      Switzerland.
FAU - Schmidt, Joerg
AU  - Schmidt J
AD  - Cell and Gene Therapies, Novartis Pharma, Basel, Switzerland.
FAU - Ritter, Anett
AU  - Ritter A
AD  - Integrated Biologics Profiling, Novartis Pharma, Klybeckstrasse 141, Basel, 4057, 
      Switzerland.
FAU - Wilms, Burkhard
AU  - Wilms B
AD  - Integrated Biologics Profiling, Novartis Pharma, Klybeckstrasse 141, Basel, 4057, 
      Switzerland.
FAU - Laux, Holger
AU  - Laux H
AD  - Integrated Biologics Profiling, Novartis Pharma, Klybeckstrasse 141, Basel, 4057, 
      Switzerland. holger.laux@novartis.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160118
PL  - United States
TA  - Biotechnol Bioeng
JT  - Biotechnology and bioengineering
JID - 7502021
RN  - 0 (Recombinant Proteins)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
SB  - IM
MH  - Animals
MH  - CHO Cells/cytology/*metabolism
MH  - Cell Proliferation
MH  - Cricetinae
MH  - Cricetulus
MH  - Gene Expression
MH  - Gene Knockdown Techniques/methods
MH  - *Gene Knockout Techniques
MH  - Genetic Engineering/*methods
MH  - Humans
MH  - Insulin-Like Growth Factor I/*genetics
MH  - Receptor, IGF Type 1/*genetics
MH  - Recombinant Proteins/genetics
OTO - NOTNLM
OT  - CHO
OT  - Chinese hamster ovary
OT  - IGF-1
OT  - IGF-1R
OT  - ZFN
OT  - cell line engineering
EDAT- 2015/11/03 06:00
MHDA- 2016/12/15 06:00
CRDT- 2015/11/03 06:00
PHST- 2015/05/26 00:00 [received]
PHST- 2015/10/11 00:00 [revised]
PHST- 2015/10/28 00:00 [accepted]
PHST- 2015/11/03 06:00 [entrez]
PHST- 2015/11/03 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - 10.1002/bit.25877 [doi]
PST - ppublish
SO  - Biotechnol Bioeng. 2016 May;113(5):1094-101. doi: 10.1002/bit.25877. Epub 2016 
      Jan 18.