For lentiviral vectors, AAV and adenoviruses
The TRiP SystemTM maximises vector production yield and quality.
Vector yields and quality can be dramatically reduced by expression of the transgene during vector production. Additionally, the vector particle can be contaminated by the transgene protein. This makes purification more challenging, reduces product purity and raises immunogenicity concerns.
Our ’Transgene Repression in Vector Production’ (TRiP) SystemTM temporarily stops the production of the transgene protein during manufacture of vector particles.
The TRiP SystemTM can significantly improve yield and particle purity. It also enables the development of vectors carrying cytotoxic transgenes, or those that inhibit cell growth.
The TRiP SystemTM works by transfecting a plasmid encoding the bacterial tryptophan RNA-binding attenuation protein (TRAP) in production cells. A TRAP binding sequence (tbs) is inserted upstream of the transgene in the vector genome. In production cells, in excess of L-tryptophan, the TRAP protein binds to the tbs sequence and blocks translation of the transgene mRNA.
How TRiP works
The TRiP SystemTM enables production of toxic transgenes – returning titre to marker gene levels
Maunder et al. (2017) Nat Communications 8:14834
Farley (2018) Cell Gene Therapy Insights 2018; 4(10), 983-994
Intellectual Property: WO 2015/092440