Our Gene Therapy Platform

Realizing the Promise of Gene Therapy

The Challenge of AAV: Manufacturing

While the adeno-associated virus (AAV) is widely considered to be an ideal vector for gene therapy—because of its favorable tissue tropism (ability to infect a particular cell type), predictable gene expression, and low toxicity—it is notoriously challenging to manufacture AAV vectors.

The current industry-standard method for manufacturing AAV is inefficient and costly, and results in low product-yield with high proportions of empty capsids – the protein shell enclosing the genetic material to be delivered via therapy. Gene therapy holds promise for diseases emanating from deficiencies in central nervous system and muscle tissues, but these diseases can require much larger doses of therapy compared to liver-targeted approaches, amplifying the problem. Many of these diseases also have higher prevalence rates, which could multiply the demand for manufacturing at scale.

Clonal Producer Cell Line (PCL) Platform: A Line Toward the Future

At Ultragenyx, we have established a new manufacturing platform that can produce AAV vectors with increased efficiency and lower material costs than traditional methods, and at a scale that can help meet the rising demands of today’s gene therapy landscape.

At the heart of our proprietary platform is our clonal Producer Cell Line (PCL) technology. As the only clonal AAV manufacturing system, we have engineered PCLs that stably produce high yields of viable, intact AAV vectors, while maximizing the production of full AAV capsids. The cells used in our PCL platform were engineered from HeLa cells. We further modified these cells into our unique clonal PCL platform for AAV manufacturing.

Ultragenyx continues to invest in improvements to further increase the capacity and efficiency of the PCL platform for gene therapy manufacturing.

Breaking New Ground with AAV Manufacturing

Reflecting our commitment to developing and delivering more accessible AAV-based gene therapies, we have begun construction on a 100,000-square-foot manufacturing facility in Bedford, Massachusetts.

We believe this state-of-the-art facility, slated for completion in 2023, will provide us with a flexibility and control of process that can further optimize the clonal PCL platform, ultimately broadening our future partnerships and advancing our own gene therapy pipeline.

Our Clonal PCL at Work Today

Through the strength of our clonal PCL platform—greater efficiency, lower costs and commercial scalability—the great potential of AAV-based gene therapy is beginning to be realized today, as evidenced by our current partnerships:

  • Bayer is using our clonal PCL platform to produce its hemophilia A gene therapy at a 2,000-liter scale.
  • Daiichi Sankyo has selected our proprietary AAV-based gene therapy manufacturing technologies, including the PCL platform, for its internal gene therapy programs.
  • Solid Biosciences is partnering with us to advance new AAV-based gene therapies for Duchenne muscular dystrophy.

Honoring the contributions of Henrietta Lacks

In 1951, a young Black woman named Henrietta Lacks was diagnosed with cervical cancer in Baltimore, Maryland. Mrs. Lacks received treatment at then-segregated Johns Hopkins Hospital, where tissue samples were collected and replicated without her knowledge. Over the next 70 years, these cells helped scientists achieve numerous medical breakthroughs. Although Mrs. Lacks died in 1951 at the age of 31, her immortal “HeLa” cells continue to have a direct impact on modern science and on the lives of patients with rare disease.

CONTACT US

We are interested in hearing from people who, like us, are focused on improving the lives of people living with serious rare and ultra-rare genetic diseases.

Want to get in touch? Contact us