High-yield recombinant adeno-associated virus gene therapy vector production
Genetic instability of baculovirus seeds encoding adeno-associated virus Cap, Rep, and inverted terminal repeat-gene of interest is a major challenge for largescale vector production in insect cells.
By locking adeno-associated virus Rep in the baculovirus genome and inserting Cap and a therapeutic gene of interest flexibly into two independent loci, a novel baculovirus expression vector was generated.
The genomic stability profile of the baculovirus vector upon serial passaging demonstrated significant improvements, as evidenced by protein expression and next-generation sequencing.
Recombinant adeno-associated virus productions with the novel baculovirus yielded titers up to 3.5e11 genome copies/ml and cellular productivities reaching 3.5e5 vector genomes/cell.
The novel BAC6Rep system is compatible with commonly used Baculovirus Expression Vector System technologies and with both high and low multiplicities of infection strategies for recombinant adeno-associated virus production in suspension cultures.
https://www.cell.com/trends/biotechnology/fulltext/S0167-7799(26)00195-2
https://sciencemission.com/Plug-in-hybrid-baculovirus-expression-vector
