Viruses have emerged as a prime tool for gene therapy and gene editing applications. While scientists were initially skeptical of viral vectors, the startling success of the 2017 gene therapy Luxturna triggered a shift in the industry, leading to the emergence of many start-ups, each seeking ways to leverage the elusive power of viruses.
Viral vector production plays a critical role in gene therapy applications. Unfortunately, current commercial production methods are plagued with challenges and inefficiencies that lead to a lower yield. Therefore, the industry heavily relies on new techniques for viral vector production optimization. This article explores the state of the art of the gene therapy industry and the innovative techniques that scientists are developing to facilitate viral vector production optimization.
The rise of gene therapy
Gene therapy is a ground-breaking technology that aims at correcting genetic diseases by supplying functional genes to the affected cells. The first-generation vectors were based on the Adenovirus (AV) family, which stimulated a significant amount of immune responses and posed a challenge to gene-therapy applications. Despite these setbacks, companies like GlaxoSmithKline and Bluebird Bio have made significant strides, finding ways of improving virus vectors and moving the technology forward.
The evolution of the gene therapy industry has seen the emergence of new viruses as potential viral vectors for gene therapy applications. Adeno-associated viruses (AAV) and Lentivirus (LV) have emerged as popular candidates in creating efficient viral vectors. However, these viruses present a new set of challenges in viral vector production optimization.
New techniques for viral vector production optimization
viral vector process development
Optimization of viral vector production relies on improving cell culture capacity and finding cost-effective and efficient methods for recombinant protein purification. Various methods share a common aim of streamlining viral vector production, however, each disease and virus has unique production challenges that call for individualized optimization techniques.
Upstream processes in viral vector production require the production of large volumes of well-controlled animal cell lines, which can be genetically engineered to produce high yields of the viral vector. Scientists are finding ways to improve transfection and transduction, such as improving the electroporation technique, reducing toxicity in the virus-producing cells, and finding alternatives to expensive reagents and growth factors.
The optimization of downstream activities involves the development of more efficient methods of purifying the virus. Chromatography, the traditional purification method, remains inefficient for the purification of highly complex viruses like AAV, and alternative methods such as membrane-based purification and precipitation techniques are emerging. Scientists are actively exploring innovative techniques like spin filters and chromatography on silica beads to improve downstream processes.
Changing bioreactor technology
The bioreactor is the core of virus vector production, facilitating growth, and transfection of the virus-producing cells. Traditional bioreactor technology relied on spin tubes and flasks, but the emergence of sophisticated wheel bioreactors, perfusion systems, and wave bags has significantly improved the scale of viral vector production. These new systems provide greater flexibility and scalability, allowing for the commercial-scale production of viral vectors required for clinical trials and commercial applications.
Cell donation and gene editing
Stem cells provide an ideal starting point for developing new viral vectors. Stem cells are multipotent, self-renewing, and have the potential to differentiate into any type of cell in the human body. With the advances in gene editing technology, scientists can differentiate these stem cells into the desired entry cell for precise tissue targeting. By reprogramming these stem cells, scientists can create an almost unlimited supply of virus-producing cells, significantly reducing the cost of viral vector production.
Viral vector-based gene therapy is revolutionizing the way we approach medicine, offering hope to patients who were once resigned to their fate. Viral vector production optimization is a critical aspect of the gene therapy value chain, and scientists are continually exploring new ways of improving methods of production. With the emergence of new techniques and technologies, gene therapy is poised to become a critical aspect of modern medicine.