PMID- 24157712
OWN - NLM
STAT- MEDLINE
DCOM- 20150512
LR  - 20211203
IS  - 1876-4347 (Electronic)
IS  - 1871-6784 (Linking)
VI  - 31
IP  - 5
DP  - 2014 Sep 25
TI  - Understanding translational control mechanisms of the mTOR pathway in CHO cells 
      by polysome profiling.
PG  - 514-23
LID - S1871-6784(13)00132-5 [pii]
LID - 10.1016/j.nbt.2013.10.003 [doi]
AB  - The mammalian target of rapamycin (mTOR) pathway plays essential roles in the 
      regulation of translational activity in many eukaryotes. Thus, from a 
      bioprocessing point of view, understanding its molecular mechanisms may provide 
      potential avenues for improving cell culture performance. Toward this end, the 
      mTOR pathway of CHO cells in batch cultures was subjected to rapamycin treatment 
      (inhibition) or nutrient supplementation (induction) and translational activities 
      of CHO cells producing a monoclonal antibody (mAb) were evaluated with polysome 
      profiling technology. Expectedly, rapamycin induced a shift of mRNAs from 
      polysomes towards monosomes, thus reducing maximum cellular growth rate by 30%, 
      while feeding additional nutrients extended mTOR pathway activity during the 
      stationary growth phase in control batch culture, thereby contributing to an 
      increase in global translation activity by up to 2-fold, and up to 5-fold higher 
      specific translation of the heavy and light chains of the recombinant mAb. These 
      increases in translation activity correlated with a 5-day extension in cellular 
      growth and a 4-fold higher final product titer observed upon nutrient feeding. 
      This first study of the relationship between the mTOR pathway and translational 
      activity in CHO cultures provides key insights into the role of translational 
      control in supporting greater productivity, which will lead to further 
      enhancement of CHO cultures.
CI  - Copyright (c) 2013 Elsevier B.V. All rights reserved.
FAU - Courtes, Franck C
AU  - Courtes FC
AD  - Bioprocessing Technology Institute, Agency for Science, Technology and Research 
      (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore; 
      Department of Chemical and Biomolecular Engineering, National University of 
      Singapore, 4 Engineering Drive 4, Singapore 117576, Singapore.
FAU - Vardy, Leah
AU  - Vardy L
AD  - Institute of Medical Biology, Agency for Science, Technology and Research 
      (A*STAR), 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
FAU - Wong, Niki S C
AU  - Wong NS
AD  - AbbVie Pte Ltd, 8 Biomedical Grove, #03-01 Neuros, Singapore 138665, Singapore.
FAU - Bardor, Muriel
AU  - Bardor M
AD  - Bioprocessing Technology Institute, Agency for Science, Technology and Research 
      (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore.
FAU - Yap, Miranda G S
AU  - Yap MG
AD  - Bioprocessing Technology Institute, Agency for Science, Technology and Research 
      (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore; 
      Department of Chemical and Biomolecular Engineering, National University of 
      Singapore, 4 Engineering Drive 4, Singapore 117576, Singapore.
FAU - Lee, Dong-Yup
AU  - Lee DY
AD  - Bioprocessing Technology Institute, Agency for Science, Technology and Research 
      (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore 138668, Singapore; 
      Department of Chemical and Biomolecular Engineering, National University of 
      Singapore, 4 Engineering Drive 4, Singapore 117576, Singapore. Electronic 
      address: cheld@nus.edu.sg.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131022
PL  - Netherlands
TA  - N Biotechnol
JT  - New biotechnology
JID - 101465345
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*biosynthesis
MH  - CHO Cells
MH  - Cricetinae
MH  - Cricetulus
MH  - Immunosuppressive Agents/*pharmacology
MH  - Polyribosomes
MH  - Protein Biosynthesis/*drug effects
MH  - Recombinant Proteins/biosynthesis
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2013/10/26 06:00
MHDA- 2015/05/13 06:00
CRDT- 2013/10/26 06:00
PHST- 2013/04/15 00:00 [received]
PHST- 2013/09/21 00:00 [revised]
PHST- 2013/10/12 00:00 [accepted]
PHST- 2013/10/26 06:00 [entrez]
PHST- 2013/10/26 06:00 [pubmed]
PHST- 2015/05/13 06:00 [medline]
AID - S1871-6784(13)00132-5 [pii]
AID - 10.1016/j.nbt.2013.10.003 [doi]
PST - ppublish
SO  - N Biotechnol. 2014 Sep 25;31(5):514-23. doi: 10.1016/j.nbt.2013.10.003. Epub 2013 
      Oct 22.