Developing a robust and scalable platform for AAV8 production.

Area of Science:

• Biotechnology
• Gene Therapy Manufacturing
• Viral Vector Production

Background:

• Adeno-associated virus (AAV) vectors are crucial for gene therapy, necessitating robust and scalable manufacturing processes.
• Current demand for AAV vectors requires efficient and reproducible production platforms.

Purpose of the Study:

• To design and implement a scalable AAV8 production platform.
• To validate process robustness and scalability from laboratory to pilot scale.
• To optimize process economics while maintaining product quality.

Main Methods:

• Conducted three production campaigns at 2-liter and 50-liter scales.
• Evaluated upstream and downstream process parameters for consistency and yield.
• Assessed key modifications including inoculation concentration, nuclease selection, and direct chromatography loading.

Main Results:

• Achieved consistent titers and recoveries near 80% across scales.
• Validated successful scalability from 2L to 50L without loss of performance.
• Demonstrated a three-fold enrichment of full capsids, indicating higher product quality.
• Identified cost-saving modifications without impacting production.

Conclusions:

• The developed AAV8 production platform is robust, scalable, and economically viable.
• The process ensures high yields and product quality, with potential for broad application across AAV serotypes.
• Optimized bioprocessing contributes to the advancement of gene therapy manufacturing.