OXGENE Seeks to Overcome Challenges in Gene Therapy Production

The rapid advancement of gene therapies has broadened the scope of how we can treat challenging diseases. There are now over 2,000 gene therapies in the global pipeline and more than 20 currently on the market. However, these therapies are hindered by challenges in large-scale manufacturing, particularly in the production of plasmids - which house the therapeutic gene of interest, and which are contained within the viral vectors that actually deliver the gene.

As the demand for gene therapies grows, companies are in a competitive race to develop manufacturing technologies that can streamline production, reduce costs, and accelerate turnaround times. Despite significant investments in the gene therapy field, the development of large-scale manufacturing technologies has not kept pace with the therapeutic advancements. The complexity of gene therapy development, involving viral particles and cell lines, is a significant challenge in achieving consistent production. Unlike conventional drug manufacturing processes, the smallest change in production conditions can lead to significant variations in the gene therapy end product.

One of the primary obstacles is the use of plasmids in viral vector production. Plasmids are small, circular pieces of DNA. In nature, plasmids are found in microbes, such as bacteria. They are relatively easy to manipulate and can be constructed to encode genes of interest. As such, they are a critical raw material for many therapeutic modalities. Producing plasmids at a Good Manufacturing Practice (GMP) level, as required by regulatory authorities, is complex and expensive. The limited global availability of GMP-grade plasmids further exacerbates the challenge. Furthermore, plasmids exhibit genetic instability, making them susceptible to unwanted genetic changes during the scaling process.

In response to these challenges, OXGENE, a WuXi Advanced Therapies (WuXi ATU) company, have developed TESSA™ and XLenti™. These technologies offer innovative alternatives to traditional plasmid-based approaches. TESSA™ leverages a modified adenoviral vector for scalable adeno-associated viral vector manufacturing, eliminating the need for plasmids. XLenti™ integrates DNA into cells to produce lentiviral vectors without introducing new plasmids. WuXi ATU is adapting its facilities to manufacture TESSA™ vectors and recombinant adeno-associated viral vectors at a GMP level.

This innovation represents an important step forward in the goal of optimizing large-scale gene therapy production in order to make it more accessible and cost-effective. By overcoming the limitations associated with plasmids and introducing scalable, cost-effective technologies, the industry is poised to make gene therapies available to a broader patient population, offering hope for those with difficult-to-treat diseases.