Recombinant adeno-associated viruses (rVVV) is small nonenveloped virus widely used as a gene transfer vehicle for in-vivo gene therapies.  To date, generating vector quantities sufficient to meet clinical demand is still a hurdle when using the current production systems.  AskBio has developed an intensified manufacturing process platform focusing on increasing cell densities and higher product rAAV yields. 

Increasing the speed at which gene therapies can be manufactured and introduced into the clinic is critical to realizing their potential. To successfully do this, the development of a “plug and play” process and platform, created by leveraging platform knowledge, is crucial. By taking this approach, an organization can help to rapidly and effectively build out a robust gene therapy pipeline.

AAV-based gene therapy products have demonstrated promising results in clinical trials,but their manufacturing costs are so high that these treatments may not be affordable for most of the patients. To increase AAV vector yields, LogicBio optimized the plasmids used for suspension HEK293 cell transfection. When combined with a novel transfection reagent, the vector titers were increased by 20 to 25 times, resulting in a significant drop of the cost of goods.

Our cGMP production suites and single-use systems will allow the production of multiple products simultaneously at up to 3,000-liter bioreactor scale. We are developing reliable and robust production systems that can deliver higher amounts of AAV product per batch.

The academic-based Clinical Vector Core (CVC) at the Children’s Hospital of Philadelphia has a 17-year track record in pre-clinical and clinical grade viral vector manufacturing for early phase clinical trials. The growth of the field has created unique challenges driven by the need for more and larger products, progression of studies to later phases of development, increased involvement of investors and industry, and increase in international collaborations and regulatory scrutiny. In this presentation we discuss challenges and bottlenecks for academic-based CMOs.

Recombinant adeno-associated virus (AAV) and lentivirus (LV) are key components in many gene and cell therapies designed to treat a vast array of human diseases. We will discuss optimization strategies for maximizing AAV and LV titers through transient transfection of adherent and suspension HEK 293 cells for both small- and large-scale processes. Attendees will also learn how VirusGEN® GMP AAV and LV Kits support gene and cell therapy researchers from R&D through commercial manufacturing.

The use of adeno-associated virus as a vector for gene therapies continues to grow. Upstream production yields have lagged the clinical demand, and production remains a significant barrier to wide adoption. This talk will detail our journey through the development of a high-yielding AAV production process and the learnings we had along the way.

Gene therapy has an increased demand on full rAAV particles by high clinical doses. AEX is commonly used to separate empty and full particles by exploiting the difference in surface charges. Here we report several improvements to an existing AEX method to enrich full rAAV ratio. High throughput screening system and PAT tools were utilized to enable rapid process development.

AAV titer, empty/full ratio, and aggregation state are critical readouts to any AAV production process. Stunner’s dye-free, label-free, and standard-free AAV quant delivers it all using just 2 µL of sample, in less than a minute - way faster than AUC, ELISA and ddPCR. Learn how Stunner’s hassle-free AAV characterization can help optimize your process.

The use of lentiviral vectors in cell therapies require the manufacture at large scale of high quality material to enable efficient cell transduction. This work discuss the main challenges lentiviral vector cell therapies face and present strategies and novel technologies to be adopted to enable effective manufacture as well as cell transduction. of cells.

Like many in the industry, our group has recently made the transition from adherent cells to suspension cells for the production of AAV. This talk will focus on the major challenges we have faced during this transition and how we have overcome them, with a focus on product yields and functionality, host-cell impurities, and the impact of specific cell lines.

Recombinant adeno-associated virus (rAAV) has emerged as a dominant gene-delivery vector of choice. Despite numerous advances in the clinic, the efficiency and cost of producing rAAV drug product to meet a rapidly growing industry has significant room for improvement. AskBio has developed a model for advancing multiple clinical programs, with an emphasis on establishing early benchmarks in manufacturing feasibility, while focusing on continuous process development and improvements to large-scale manufacturing.

Adeno-associated virus (AAV) is an attractive delivery vehicle in gene therapy attributed to its mild immune response and ability to deliver its genome into a range of host cells. This presentation will discuss a method to measure the following three important AAV quality attributes (QAs): 1) total number of viral capsid particles; 2) relative capsid content (e.g., ratio of empty and full capsids); and 3) percentage of monomer or aggregates.

During the late stage development, the scale down model (SDM) becomes a critical tool for process characterization (PC). In this presentation, strategy for SDM development, qualification, and process characterization will be shared for HEK293 transient transfection system. In addition to monitoring cell growth performance, product titer and quality, other atline/offline analytical tools were employed to further characterize the transfection complex.

Recombinant adeno-associated virus (rAAV) has emerged as a leading gene-delivery vector of choice. Despite numerous advances in the clinic, the efficiency and cost of producing rAAV drug product to meet a rapidly growing industry has significant room for improvement. AskBio has developed a model for advancing multiple clinical programs, with a focus on continuous upstream and downstream process development and improvements to large-scale manufacturing.

As new AAV gene therapy projects enter CMC development it is important to understand the extent to which novel AAV serotypes are compatible with the current production platform. Introducing a new serotype to the platform often poses challenges in early development that require optimization of the platform to fit the new serotype. In some cases, changes made to the platform to accommodate a non-conforming AAV serotype add value as the changes can become “platformized” and further improve the current platform. This presentation will walk through the development activities involved in assessing an AAV harvest platform fit for a new AAV capsid serotype, the associated risk/gap analysis, and the process development conducted to ensure high recovery of AAV and reduction of impurities.