This work presents a next-generation plasmid platform engineered to enhance the efficiency, robustness, and scalability of AAV production. By integrating optimized genetic elements with a modular design, the platform increases vector yield and quality while reducing process complexity. This streamlined approach enables more reliable performance across manufacturing scales and offers a transformative solution to meet the growing demand for high-quality AAV therapeutics.

This presentation will highlight CMC and bioprocessing considerations for advancing a next-generation AAV capsid designed for intravenous delivery to the brain. Using case studies, the talk will explore process development, analytical strategies, and manufacturing approaches supporting novel vector platforms. Broader themes around scalability, product quality, and preparing emerging AAV technologies for clinical manufacturing. as programs move toward first-in-human studies in 2026, will also be discussed.

This presentation will explore the evolving landscape of genome-editing therapeutics and the key considerations required to advance these products toward the clinic. As diverse editing platforms emerge, developers must address challenges spanning design, delivery, manufacturing, and regulatory strategy. The talk will discuss common development considerations and highlight approaches used to evaluate risk, support product characterization, and align CMC strategies with the unique requirements of genome-editing modalities.

Midstream bioprocessing critically determines the recovery and purity of gene therapy products. This presentation examines how midstream decisions (harvest timing, depth filtration, tangential-flow filtration) set the stage for successful purification. We discuss the impact of midstream processing on chromatographic operations and the resulting quality attributes of adeno-associated virus, lentivirus, and adenovirus. Leveraging process optimization frameworks, we demonstrate how midstream excellence enables robust purification workflows that ensure therapeutic efficacy and safety.

This study evaluates alternative nucleases/methods for the harvest of AAV vectors after upstream production. By analyzing the impact of various nucleases/methods under diverse conditions, we assessed process performance, product quality, and downstream Cost of Goods (CoG). Our findings provide critical insights for optimizing the harvest process, balancing robust process with economic efficiency in gene therapy manufacturing.

In Sanofi’s AAV manufacturing platform, the harvest process typically involves a flocculation step, where mixing plays a critical role. Developing a robust mixing scale‑down model is essential. Floc formation dynamics were characterized in real time using EasyViewer technology. The developed scale‑down model demonstrated excellent predictive performance. Implementation of the optimized flocculation conditions resulted in a two‑fold increase in depth filter throughput.

AAV vectors are a leading platform for in vivo gene delivery, but production is hindered by empty or partially filled capsids that compromise therapeutic efficacy. These quality attributes require close monitoring, yet current analytical methods are slow, costly, and low-throughput. To address this gap, we developed an in-line quantum cascade laser mid-infrared spectroscopy (QCL-MIDIR) platform combined with Partial Least Squares Regression (PLSR) models to characterize AAV9 particles. The system accurately predicts concentration and capsid-filling status, with a detection limit of 9.79E12 cp/mL and sensitivity down to 18.4% non-empty capsids, enabling rapid, high-throughput analysis during development.

Lentiviral vectors (LVs) are widely used for ex vivo CAR T cell therapy, but patient-specific manufacturing is complex and costly. Recently, LVs engineered to transduce T cells in vivo following intravenous administration have entered clinical studies as off-the-shelf products. LVs used intravenously require higher purity standards. Accordingly, we present process development efforts to reduce residual DNA and optimize yields, emphasizing impurity–LV interactions critical for robust manufacturing.

Manufacturing AAV vectors via transient transfection of HEK293 cells depends on timely delivery of transfection complexes to bioreactors. We found plasmid–reagent complex size, which changes with incubation, influences productivity overall. To address this constraint, we developed a method to arrest complex growth at the optimal size, enabling storage up to 2 days with less than 20% change in vector genome titer and less than 5% change in full capsids.

Gene therapy is shifting our perspective on disease treatment with a single-dose life-changing administration. Seamless design, execution, tech transfer, and finetuning of a multi-product clinical facility is one of the key challenges in the field. The ultimate goal is to bring rapidly and with the highest compliance.

Advancing rAAV gene therapy programs to commercialization demands robust, well-characterized manufacturing processes aligned with regulatory expectations. This talk will present a platform-driven CMC framework integrating comprehensive process mapping and associated risk assessments (e.g., FMEA), scale-down models, and process characterization studies utilizing DoEs—to understand the design space, determine CPPs, and define a reliable control strategy that supports regulatory submission and commercial readiness.