Unravelling Molecular Insights for Enhanced rAAV Production in Gene Therapy

From Left: Dr Bi Xuezhi, Dr Alok Tanala Patra, Dr Evan Tan, Dr Ng Say Kong, Dr Kok Yee Jiun

 

Science

This research aims to understand how cells behave when producing gene therapy vectors, which are essential for treating genetic diseases. By investigating the molecular and cellular responses during this process, scientists seek to enhance the production of these vectors, addressing challenges in large-scale manufacturing and ultimately improving the effectiveness of gene therapy treatments. By better understanding this process, they hope to make gene therapy treatments more affordable and effective for patients.

 

Societal Impact

The findings from this study could have a significant impact on research, the biotherapeutics industry, and patients. Understanding the molecular and cellular responses underlying viral vector production could guide the development of improved processes for the manufacturing of cell and gene therapies. This could make such therapies more affordable, enhance treatment outcomes, and expand access to healthcare services, ultimately improving patient care.

 

Technical Summary

Recombinant adeno-associated viruses (rAAVs) have become the preferred choice for gene therapy due to their efficient and targeted delivery with minimal side effects. However, a major hurdle lies in improving their production for high viral titers containing the desired therapeutic gene. This study addressed this challenge by uncovering the underlying cellular mechanisms in HEK293 cells during rAAV production. The researchers employed SWATH-MS proteomics to map the temporal changes in both molecular and cellular activity during rAAV production. This analysis revealed 124 host cell proteins associated with AAV replication and assembly, each exhibiting unique expression patterns under different production conditions. These findings provide valuable insights into the cellular processes governing rAAV production, paving the way for the development of more efficient and productive gene therapy strategies.

Figure 1. Insights into Cell Activity During Gene Therapy Virus Production

 

References

Patra, A.T., Tan, E., Kok, Y.J., Ng, S.K., & Bi, X. (2024). Temporal insights into molecular and cellular responses during rAAV production in HEK293T cells. Molecular Therapy: Methods & Clinical Development. https://doi.org/10.1016/j.omtm.2024.101278