Emerging Therapeutics

Using Synthetic Biology To Develop Novel Biotherapeutics

A multidisciplinary area of research, synthetic biology involves the use of genetic engineering to create new biological parts, devices, and systems, with potential applications in industries such as healthcare, agriculture, energy, and environmental science. As early as the 1960s, researchers combined advanced techniques in precision genetic engineering with rational drug development and explored approaches in synthetic biology to support development of innovative drug products. Later research shed new light on how molecular networks regulate cellular function and how gene expression…

Cell-Free Synthesis of Highly Potent Recombinant Neurotoxins: A Process Economic Feasibility Study

Since its inception four decades ago, cell-free synthesis (CFS) has been used to produce biomolecules such as RNA, DNA, peptides, and proteins (1). However, most of these applications have been in early stage research and small-scale proof-of-concept studies, with rare examples of large-scale production. The slow industrial uptake of CFS has been attributed to low productivity, which suggests an uneconomical path to large-scale manufacture. Typically, a CFS platform includes a genetic template (encoding the product of interest), chemical additives (nucleotides…

Optimizing and Intensifying ADC Aggregate Removal: A DoE Approach to Membrane Chromatography and Rapid Cycling

Antibody–drug conjugates (ADCs) represent a growing therapeutic segment of the oncology field. Five such treatments received market approval from the US Food and Drug Administration (FDA) between 2008 and 2018, whereas three were approved in 2019 and two each were approved in 2020 and 2021 (1). This disruptive technology combines highly potent small-molecule payloads with monoclonal antibodies (MAbs) to improve their specificity as cancer treatment. The antibodies deliver those toxic compounds directly to cancer cells but not to healthy cells,…

eBook: MSC-Derived Extracellular Vesicles Challenges in Production, Scale-Up, and Characterization

The discovery of extracellular vesicles (EVs) as an intercellular communication medium has led to explorations of their therapeutic potential. EVs constitute a heterogeneous mixture of several different vesicle populations that may be similar in size but different in content, or vice versa. The vesicles can contain RNAs and proteins as well as DNAs and lipids as biological cargoes. Those cargoes can exist either intraluminally within EVs or on their surface, adding complexity to analytical considerations. EVs are classified into subpopulations…

BioProcess Insider Interview: Brian Finrow, Lumen Biosciences

Moderator: Dan Stanton, Co-founder and Editor, BioProcess Insider. Featuring: Brian Finrow, Co-founder & CEO, Lumen Biosciences. Although Chinese hamster ovary (CHO) cells remain the biopharmaceutical industry’s preferred expression system for antibody production, companies such as Lumen Biosciences are seeking out alternative hosts. Finrow cautioned that CHO cells sometimes complicate efforts to develop scalable and cost-effective manufacturing processes. For gastrointestinal (GI) indications such as Clostridium difficile infection and Crohn’s disease, spirulina, a biomass composed of cyanobacteria and their cellular by-products, could…

Delivering on the Promise of Bispecifics: State-of-the-Art Bispecific Antibody Development

Bispecific antibodies (bsAbs) have transformed the field of immunotherapy. However, moving these life-changing therapeutics from the bench to the clinic can be time-consuming and costly. Further, challenges such as aggregation, degradation, fragmentation, and denaturation may ultimately hinder a program from advancing to the clinic. Partnering with a CDMO with relevant experience and technologies can be critical for safely and cost-effectively manufacturing bispecific antibodies. With Selexis’s cell line technology and KBI Biopharma’s manufacturing and analytics, we lead the industry in technologies…

Increasing Dynamic Binding Capacity of Oligo(dT) for mRNA Purification: Experimental Results Using CIM 96-Well Plates

Messenger RNA (mRNA) emerged as a powerful therapeutic tool for treatments in gene therapy, oncology, and infectious diseases, as recently demonstrated by vaccines against Covid-19. mRNA is produced by an enzymatic reaction that can be rapidly designed and scaled-up, and the platform is highly adaptable to different targets. One of the greatest challenges in mRNA production is the removal of process-related impurities stemming from in vitro transcription (IVT) reaction, such as residual nucleotide triphosphates, DNA template, enzymes, abortive transcripts. Affinity-based…

Managing Manufacturing Requirements for Live Biotherapeutics

In 2018, Synlogic explored options for producing clinical-trial material for its lead programs, including a candidate therapy for the rare metabolic disease phenylketonuria (PKU). Like other emerging drug developers, the company evaluated the merits of outsourcing manufacturing to third parties. However, Synlogic leverages synthetic biology tools to design and develop therapeutics based on genetically engineered microbes. Thus, it also needed to consider requirements specific to live biotherapeutics. Late in 2018, Synlogic announced plans to establish its own current good manufacturing…

Pseudomonas fluorescens: Cell-Line Development of a Commercially Proven Platform for Biopharmaceutical Manufacturing

A number of factors contribute to delivering a robust, highly productive, and reliable process for manufacturing a therapeutic protein. They begin with a cell-host system and a gene-expression strategy that determine a developer’s ability to optimize growth and expression titers. But for many therapeutic proteins, initial attempts to develop a production process are based on evaluation of limited factors and tend to yield only small quantities or poor product quality. Automation can enable parallel building and expression screening of diverse…

The Evolution of Predictive Toxicology: Improving Predictivity Using New-Approach Methodologies

A pharmaceutical’s approval for commercial distribution is contingent on submission of pharmacological and toxicological safety data as defined by regulatory agencies such as the US FDA and ICH. Guidances state that such data can come from in vivo or in vitro studies. The current paradigm works well for collecting critical data about, e.g., a drug’s pharmacological effects and mechanism of action (MoA). However, increasing evidence points to current methods’ inadequacy for predicting a drug’s risks to human patients. Such limitations…