Reprogramming of HEK293 for High-Yield AAVs

June 23, 2025

Reprogramming of HEK293 for High-Yield AAVs

We offer a collaborative project that combines genome-scale metabolic modeling with targeted multi-omics analyses to optimize gene therapy manufacturing. By systematically identifying and resolving bottlenecks in HEK293 cells, we boost viral vector yield and quality - advancing scalable and efficient gene therapy solutions.

Background

Gene therapy is revolutionizing medicine, but scalable, cost-efficient manufacturing remains a major hurdle. HEK293 cells are the workhorse for viral vector production, yet yields are often low, and the ratio of full-to-empty capsids remains suboptimal. Current process improvements rely heavily on trial-and-error. While single-omics studies have shed some light on cellular behavior, an integrated, systems-level approach is still missing. A predictive, data-driven strategy could unlock major gains in vector quality and productivity – moving gene therapy closer to true industrial scalability.

Technology

Our technology combines condition-specific genome-scale metabolic modelling with multi-omics data to uncover hidden metabolic bottlenecks and regulatory nodes. This approach recently pinpointed pseudohypoxia and HIF1α signalling as key barriers in HEK293 cells – where targeted inhibition more than doubled capsid output. Beyond mapping limitations, our models guide rational strain engineering and process design, offering a powerful tool for optimizing viral vector manufacturing.

Offer

We co-develop next-generation AAV production platforms using our multi-omics integrated genome-scale metabolic modelling framework. Our expertise includes model construction, data integration, and experimental validation. By joining forces, you gain access to:

Tailored genome-scale metabolic modelling of proprietary or commercial HEK293 derivatives.
Integrated omics profiling under relevant bioprocess conditions
Predictive simulations to guide genetic, media, and process optimization.
In silico screening of intervention strategies before experimental trials to reduce lab time and save costs.

This approach accelerates the development of high-yield, high-quality AAV manufacturing systems with reduced cost of goods.

IP generated in a project with acib can be fully transferred. We are looking for industrial partners to co-develop HEK293-based AAV production platforms tailored to your vector design and manufacturing requirements.

Experts:

Leopold Zehetner, Jürgen Zanghellini

Development status:

Status of the project proposal – Technology Readiness Level 4 (Technology validated in lab)

Keywords:

HEK293, Metabolic Model, Metabolic Flux Analysis, Omics Integration, AAV Production, Viral Vector, Capsid Quality, Cell Line Productivity, Bioprocess, HIF1α

HEK293 Cells image by Gemini

For more information please contact

Dr. Martin U. Trinker
Director Business Development & Fundraising
Krenngasse 37
8010 Graz
+43 316 873 9316