Manufacturing of recombinant adeno-associated virus (rAAV) viral vectors remains challenging, with low yields and low full:empty capsid ratios in the harvest. To elucidate the dynamics of recombinant viral production, we develop a mechanistic model for the synthesis of rAAV viral vectors by triple plasmid transfection based on the underlying biological processes derived from wild-type AAV. The model covers major steps starting from exogenous DNA delivery to the reaction cascade that forms viral proteins and DNA, which subsequently result in filled capsids, and the complex functions of the Rep protein as a regulator of the packaging plasmid gene expression and a catalyst for viral DNA packaging. We estimate kinetic parameters using dynamic data from literature and in-house triple transient transfection experiments. Model predictions of productivity changes as a result of the varied input plasmid ratio are benchmarked against transfection data from the literature. Sensitivity analysis suggests that (1) the poorly coordinated timeline of capsid synthesis and viral DNA replication results in a low ratio of full virions in harvest, and (2) repressive function of the Rep protein could be impeding capsid production at a later phase. The analyses from the mathematical model provide testable hypotheses for evaluation and reveal potential process bottlenecks that can be investigated.

This paper illustrates how supply chain (SC) analytics could provide strategic and operational insights to evaluate the risk-based allocation of regulatory resources in food SCs, for management of food safety and adulteration risks. This paper leverages data on 89,970 tests of aquatic products extracted from a self-constructed data set of 2.6 million food safety tests conducted by the China Food and Drug Administration (CFDA) organizations. The integrated and structured data set is used to conduct innovative analysis that identifies the sources of adulteration risks in China’s food SCs and contrasts them with the current test resource allocations of the CFDA. The analysis highlights multiple strategic insights. Particularly, it suggests potential gaps in the current CFDA testing allocation by SC location, which is heavily focused on retail and supermarkets. Instead, the analysis indicates that high-risk parts of the SC, such as wholesale and wet markets, are undersampled. Additionally, the paper highlights the impact that SC analytics could have on policy-level operational decision making to regulate food SCs and manage food safety. The hope is that the paper will stimulate the interest of academics with expertise in these areas to conduct more work in this important application domain. This paper was accepted by Charles Corbett, operations management.