ICM develops its gene therapies based on AAV gene delivery platform by optimizing therapeutic gene expression cassettes and capsid serotype. ICM’s OASys platform expedites efficient development of multiple gene therapy pipelines.

ICM adopts Baculovirus Dual Vector Method (BDVM) to produce recombinant AAV therapeutic vector.

Two types of baculovirus are employed in BDVM. One carries therapeutic transgene, and the other provides Rep/Cap genes for AAV genome replication and capsid protein expression, respectively. By dual-infection of these two baculoviruses, the rAAV is produced in Sf9 insect cells.

For scale-up to large quantity production, BDVM permits reproducible and high-yield AAV manufacturing compared to the classical approach with triple-transfection of transgene, Rep/Cap and helper-gene plasmids to HEK293 cells.

The AAV production system using HEK293 cells has several technical risks. First, the impurities from HEK293 cells could be problematic because they are potentially immunogenic. Second, endotoxin contamination is an unavoidable issue, since the plasmids for transfection are produced in bacterial cultures. Third, residual helper viruses such as adenovirus or herpes simplex virus are concerns, as they are infectious to human cells.

On the other hand, BDVM does not use materials originated from human cells and bacteria in the final production stages of rAAV. Furthermore, helper virus is not involved in BDVM production of rAAV. Taken together, very low risk of impurities from human, bacteria, or human infectious viruses is a great advantage of BDVM.