2021

Toward the Point of Care: Flexibility and Decentralization Are Key to Making Autologous Therapies More Readily Available

Part of the advanced therapy medicinal products (ATMPs) class of therapeutics, cell and gene therapies (CGTs) can be either autologous, using the patient’s own cells, or allogeneic, using master banked donor cells. Global biotechnology company Orgenesis focuses on autologous therapies, with processes and systems developed for closed and automated processing that have been validated for regulatory-compliant production at the point of care for patient treatment. This technology could help overcome the limitations of traditionally cost-prohibitive CGT manufacturing methods that do…

Measuring Viral Titer in AAV-Mediated Gene Therapy Using a PCR Technique for Absolute Quantitation

Gene therapies have reemerged as promising treatments to a number of genetic illnesses. Nearly 400 gene therapy clinical trials are recruiting or ongoing in the United States for diseases such as hemophilia and spinal muscular atrophy (1). The primary vehicles used today to deliver such therapies to patients’ cells are viral vectors such as adenoassociated viruses (AAVs), but producing biologically active vectors for gene therapy can be problematic. One difficulty is generating vectors at the correct concentration to yield a…

Analytical Methods for Cell Therapies: Method Development and Validation Challenges

Advanced-therapy medicinal product (ATMP) characterization and analysis play important roles in providing chemistry, manufacturing, and controls (CMC) information for regulatory applications as well as in supporting product-release and stability studies. Each type of advanced therapy presents different analytical development challenges, so each requires specific characterization, potency, purity and identity assays. Variability in cells and among patients, multiple and complex mechanisms of action (MoAs), a general lack of readily available reference materials, and complicated analytical methods and instruments underlie the major…

Ligand-Based Exosome Affinity Purification: A Scalable Solution to Extracellular Vesicle Downstream Bottlenecks

Novel therapeutics based on extracellular vesicles (EVs) recently passed a critical development milestone. During 2020, some of the first experimental EV products developed by biopharmaceutical companies entered human clinical trials (1–3). EVs are nanometer-sized, lipid-wrapped spheres released by almost every cell type in the human body. EVs are loaded with a cargo of proteins, lipids, and RNA, and they are tagged with surface markers that favor uptake by target cells. Thus, EVs are a key mode of cell-to-cell communication (4).…

The Promise of Artificial Intelligence in Healthcare

The term artificial intelligence (AI) has become pervasive in conversations about the future of healthcare. AI has the potential to transform medicine through novel models of scientific discovery and healthcare delivery, ultimately leading to improved individual and public health. Yet misunderstanding and miscommunication abound. Thus, concepts related to AI need to be defined and explained to elevate our general level of understanding and our discourse around the topic. The Promise of AI in Healthcare AI has been studied by computer…

A Complete Solution for MSC Therapy Workflows: Cell Scale-Up, Cryopreservation, and DMSO Removal

Mesenchymal stem cells (MSCs) are used frequently for cell therapy applications. As multipotent cells, they can differentiate into other lineages such as adipocytes, osteocytes, and chondrocytes. Additionally, they are known to secrete trophic factors that can play important roles in immunoregulation. Although MSCs can be isolated from several different tissue sources, those derived from bone marrow commonly are studied because they are easy to access in quantities large enough for therapeutic dosing (2 × 106 cells/kg of body weight). Still,…

Validation of a Next-Generation Single-Use Turbidity System

Turbidity describes the relative clarity of a liquid as the result of suspended solids. Instruments that measure turbidity typically use a beam of light to detect particles by measuring the difference between the amount of light emitted from the light source and the amount that is received by a detector. Such measurements are affected by the size, shape, and number of particles in a sample of liquid because those solids scatter the incoming light, which provides an apparent absorbance that…

Overcoming Obstacles in AAV Viral Vector Manufacturing

Rapidly growing interest in gene therapy has led to the need for more cost-effective and scalable viral-vector manufacturing platforms. Adenoassociated virus (AAV) has become a vector of choice because of its safety profile (nonpathogenic infection). In addition, AAV cannot replicate on its own and is not integrated directly into the host genome. AAV vector manufacturing using human embryonic kidney (HEK) cells in either adherent or suspension mode includes several typical processing steps: cell expansion, plasmid transfection, viral-vector production, cell lysis,…

Eliminating the Analytical Bottleneck in Production and Purification of mRNA

COVID-19 has focused a spotlight on the ability of mRNA technology to accelerate vaccine development and approval (1). That same technology can hasten development and approval of other therapeutic classes, including cancer immunotherapy, protein replacement, and gene therapy. Fulfilling those opportunities imposes significant challenges on process developers and manufacturers to improve existing processes. Scale-up to produce millions of doses (tens of kilograms) compounds those challenges. Furthermore, every step of the journey requires high-performance analytical methods, to ensure patient safety and…

Space Travel Rockets Mitochondria’s Central Role into the Spotlight

Mitochondria originated millions of years ago, likely when a eukaryotic cell incorporated a bacterium. Thus, mitochondrial DNA strands are 200,000× smaller than those from a cell’s nucleus. Depending on cell type, thousands of mitochondria can reside within the walls of one human cell. The scientific community long has considered these organelles to be cellular “energy factories.” But their centrality to human health and disease only now has come to light. In a breakthrough study published in Cell (1), biologists collaborated…