Screen of more than 2,400 microRNAs identifies multiple candidates that significantly enhance vector productivity without compromising quality attributes.
Munich, Germany – November 5, 2025 – Ascend Advanced Therapies scientists have published a study in New Biotechnology identifying microRNAs (miRNAs) that improve recombinant adeno-associated virus (rAAV) production in HEK293 cells.
The paper, titled “A human genome-wide screen identifies miRNAs to increase recombinant Adeno-associated virus production in HEK293 cells,” describes the first systematic identification of microRNAs capable of boosting rAAV yields in HEK293 cells. Screening more than 2,400 human miRNAs, the researchers discovered 144 candidates that improved functional rAAV titers, with six validated across different experimental formats.
Among these, hsa-miR-125a-5p significantly enhanced vector productivity without compromising quality attributes such as genome integrity or host cell DNA impurity levels.
“This work demonstrates that microRNA-based cell engineering can unlock new efficiencies in AAV manufacturing, potentially lowering the cost and increasing the scalability of gene therapies,” said Dr. Markus Hörer, CSO at Ascend.
The study’s findings pave the way for the development of engineered HEK293 producer cell lines expressing selected miRNAs, offering a promising route toward more efficient and consistent AAV vector production for clinical and commercial applications. Additionally, many identified candidates significantly down-regulate AAV production. Downregulation of those candidates that are abundantly expressed in production cells has the potential to further boost AAV yields.
The research was conducted by Ascend Advanced Therapies (Munich, Germany) in collaboration with the research group of Prof. Kerstin Otte from Biberach University of Applied Sciences – world-leading experts in this field. Data supporting the findings are under patent protection (PCT/EP2025/059386, filed April 6, 2025).
The complete publication is available through Open Access and can be accessed here:
https://www.sciencedirect.com/science/article/pii/S1871678425001050
