PMID- 28345582
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20181211
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 8
DP  - 2017 Mar 27
TI  - Enhancing titres of therapeutic viral vectors using the transgene repression in 
      vector production (TRiP) system.
PG  - 14834
LID - 10.1038/ncomms14834 [doi]
LID - 14834
AB  - A key challenge in the field of therapeutic viral vector/vaccine manufacturing is 
      maximizing production. For most vector platforms, the 'benchmark' vector titres 
      are achieved with inert reporter genes. However, expression of therapeutic 
      transgenes can often adversely affect vector titres due to biological effects on 
      cell metabolism and/or on the vector virion itself. Here, we exemplify the novel 
      'Transgene Repression In vector Production' (TRiP) system for the production of 
      both RNA- and DNA-based viral vectors. The TRiP system utilizes a translational 
      block of one or more transgenes by employing the bacterial tryptophan RNA-binding 
      attenuation protein (TRAP), which binds its target RNA sequence close to the 
      transgene initiation codon. We report enhancement of titres of lentiviral vectors 
      expressing Cyclo-oxygenase-2 by 600-fold, and adenoviral vectors expressing the 
      pro-apoptotic gene Bax by >150,000-fold. The TRiP system is transgene-independent 
      and will be a particularly useful platform in the clinical development of viral 
      vectors expressing problematic transgenes.
FAU - Maunder, H E
AU  - Maunder HE
AD  - Research Department, Oxford BioMedica Ltd., Windrush Court, Transport Way, Oxford 
      OX4 6LT, UK.
FAU - Wright, J
AU  - Wright J
AD  - Research Department, Oxford BioMedica Ltd., Windrush Court, Transport Way, Oxford 
      OX4 6LT, UK.
FAU - Kolli, B R
AU  - Kolli BR
AD  - Research Department, Oxford BioMedica Ltd., Windrush Court, Transport Way, Oxford 
      OX4 6LT, UK.
FAU - Vieira, C R
AU  - Vieira CR
AD  - Research Department, Oxford BioMedica Ltd., Windrush Court, Transport Way, Oxford 
      OX4 6LT, UK.
FAU - Mkandawire, T T
AU  - Mkandawire TT
AD  - Research Department, Oxford BioMedica Ltd., Windrush Court, Transport Way, Oxford 
      OX4 6LT, UK.
FAU - Tatoris, S
AU  - Tatoris S
AD  - Research Department, Oxford BioMedica Ltd., Windrush Court, Transport Way, Oxford 
      OX4 6LT, UK.
FAU - Kennedy, V
AU  - Kennedy V
AD  - Research Department, Oxford BioMedica Ltd., Windrush Court, Transport Way, Oxford 
      OX4 6LT, UK.
FAU - Iqball, S
AU  - Iqball S
AD  - Research Department, Oxford BioMedica Ltd., Windrush Court, Transport Way, Oxford 
      OX4 6LT, UK.
FAU - Devarajan, G
AU  - Devarajan G
AD  - Research Department, Oxford BioMedica Ltd., Windrush Court, Transport Way, Oxford 
      OX4 6LT, UK.
FAU - Ellis, S
AU  - Ellis S
AD  - Research Department, Oxford BioMedica Ltd., Windrush Court, Transport Way, Oxford 
      OX4 6LT, UK.
FAU - Lad, Y
AU  - Lad Y
AD  - Research Department, Oxford BioMedica Ltd., Windrush Court, Transport Way, Oxford 
      OX4 6LT, UK.
FAU - Clarkson, N G
AU  - Clarkson NG
AD  - Research Department, Oxford BioMedica Ltd., Windrush Court, Transport Way, Oxford 
      OX4 6LT, UK.
FAU - Mitrophanous, K A
AU  - Mitrophanous KA
AD  - Research Department, Oxford BioMedica Ltd., Windrush Court, Transport Way, Oxford 
      OX4 6LT, UK.
FAU - Farley, D C
AU  - Farley DC
AD  - Research Department, Oxford BioMedica Ltd., Windrush Court, Transport Way, Oxford 
      OX4 6LT, UK.
LA  - eng
PT  - Journal Article
DEP - 20170327
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Codon)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 63231-63-0 (RNA)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Bacillus subtilis/genetics
MH  - Codon
MH  - Cyclooxygenase 2/genetics
MH  - *Genetic Vectors
MH  - Green Fluorescent Proteins/genetics
MH  - HEK293 Cells
MH  - Humans
MH  - Protein Biosynthesis
MH  - RNA/genetics
MH  - Transgenes
PMC - PMC5378976
COIS- The work described was fully funded by Oxford BioMedica Ltd., and all authors at 
      the time of submission, except T.T.M. and S.T., were employees and hold stock or 
      stock options within the company.
EDAT- 2017/03/28 06:00
MHDA- 2018/12/12 06:00
PMCR- 2017/03/27
CRDT- 2017/03/28 06:00
PHST- 2016/12/16 00:00 [received]
PHST- 2017/02/03 00:00 [accepted]
PHST- 2017/03/28 06:00 [entrez]
PHST- 2017/03/28 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2017/03/27 00:00 [pmc-release]
AID - ncomms14834 [pii]
AID - 10.1038/ncomms14834 [doi]
PST - epublish
SO  - Nat Commun. 2017 Mar 27;8:14834. doi: 10.1038/ncomms14834.