Demand is on the rise for recombinant adeno‐associated viruses (rAAVs) used in the development of gene therapies. Late in October, Amy Shen, PhD, a principal scientist in the department of cell culture bioprocess engineering at Genentech, and her colleagues reported: “The gene therapy field has advanced in recent years with five recombinant [adeno-associated virus-based products] winning Food and Drug Administration (FDA) approval.” Beyond approved products, many more drugs based on rAAVs are likely in development. Keeping up with the demand for rAAVs could be challenging.
As recently noted by three scientists from the U.K.-based University of Oxford and Oxgene: “Efficient manufacture of recombinant adeno-associated virus (rAAV) vectors for gene therapy remains challenging.”
Human embryo kidney 293 cells
So far, most of the development of rAAV-based therapies is based on human embryo kidney 293 (HEK293) cells, according to the Genentech team. So, they tried Chinese hamster ovary (CHO) cells—a bioprocessing favorite—because, they noted, “there is no report to our knowledge describing the use of CHO cells for rAAV production.” In a comparison of rAAV-based process with HEK293 and CHO cells, the Genentech team produced comparable levels of viral particles.
Based on these results, the Genentech scientists concluded: “To our knowledge, this is the first report showing the successful production of rAAV in CHO cells using a helper‐free approach and sheds light on ultimately utilizing CHO for rAAV production to enable future gene therapies.”
HEK273 and CHO cells, however, are not the only options in manufacturing rAAV-based drugs. For example, scientists from Avirmax Biopharma, Stanford University, and the University of Delaware, compared HEK293 and insect cells—Sf9 cells from the fall army worm (Spodoptera frugiperda)—in manufacturing rAAV-based biotherapeutics. As a result, these scientists noted: “Sf9-rAAV may be preferred over HEK293-rAAV for advantages in yields, full/empty ratio, scalability, and cost.”
Although rAAV-based methods of producing biotherapeutic continue to grow, the best cells to use remains unknown. Over time, the bioprocessing industry might settle on a favorite source of cells for making these gene therapies or maybe various cell types will be used. As the Genentech scientists pointed out, however, CHO “cells have been a robust host for biomolecule manufacturing for more than 35 years.” So, maybe CHO cells will win out in the search for the best method of manufacturing the rAAV-based therapeutics of tomorrow.
