Realizing Gene Therapy’s Potential: Conquering Challenges in Viral Vector Production

Several intractable, devastating diseases are becoming treatable with the advent of gene therapies. One obstacle gene therapies face is targeting delivery of therapeutic genes into cells to maximize treatment effectiveness and minimize side effects. The administration of gene therapies hinges on the use of vectors, such as adeno-associated viruses (AAV), to deliver the therapeutic genes into target cells. However, while AAVs have emerged as prime candidates for gene therapy delivery and have been heavily invested in by the pharmaceutical industry, their large-scale production is still fraught with difficulty.

Obtaining intact, packaged, and pure AAVs from cell cultures often involves a lengthy purification process with many steps, which causes substantial loss in yield. This is particularly evident during viral vector purification using affinity chromatography, which may lack specificity and result in the co-purification of empty particles, despite being scalable, high-throughput and automatable. Additionally, the characterization of AAVs can often be difficult, mainly due to challenges in obtaining operational data, especially when dealing with low sample amounts. Overcoming these hurdles is necessary for realizing the full potential of AAV-based gene therapies. Improving yield, purity, and data quality can help with this.

Improving Quality and Yield

Inconsistent packaging of viral payloads can compromise the efficacy and safety of AAVs. Density Gradient Ultracentrifugation (DGUC)[i]—a gold standard viral vector purification technique, allows efficient separation of empty and full viral particles using Density-gradient ultracentrifugation methods. The Optima XPN Ultracentrifugeby Beckman Coulter Life Sciences is tailored for small- and medium-scale operations, ensures high-purity samples, and provides enhanced yields at a 250X reduced per-sample cost compared to affinity chromatography.

Obtaining Insightful Data

Obtaining excellent, reproducible data from AAV samples is crucial for their development, but small sample sizes limits their in-depth characterization in practice. The SCIEX ZenoTOF 7600 Mass Spectrometry System provides deep insights into AAV candidates using in-depth post-translational modification characterization. It can identify process-related protein impurities and proteome-wide changes, facilitating informed decision-making at crucial stages during AAV production[i].

Overcoming the challenges in AAV purification will help maximize the benefits of gene therapy as a groundbreaking medical treatment. Contact an expert at the Life Sciences companies of Danaher Corporation to learn how innovative automation solutions can help you unlock the true potential of gene therapy.