Dübel, Stefan

Over the past three decades, the emergence of recombinant antibodies has positioned them as the fastest-growing class of therapeutic proteins and as well as crucial reagents for both diagnostics and specific research applications. The industrial production of most therapeutic antibodies currently relies on mammalian cell lines, primarily Chinese Hamster Ovary (CHO) cells, which remain the gold standard in biopharmaceutical manufacturing due to their exceptionally high production yields, robustness, regulatory acceptance, and consistent product quality. Nevertheless, new approaches using specifically adapted expression systems are emerging. These new host organisms enable the production of antibodies with posttranslational modifications that closely resemble those found in the human system, without the need for animal-derived source materials. For diagnostic and research purposes, a broad range of production systems has been developed. These include Gram-negative and Gram-positive bacteria, yeasts, filamentous fungi, insect cell lines, and transgenic plants. Additionally, smaller single domain antibodies and bispecific fragments that do not require glycosylation can be successfully produced in bacteria for therapeutic applications. Some of these molecules have already been approved by regulatory authorities in the European Union and the United States, and several more are currently in clinical trials. This review therefore focuses on the broad and evolving landscape of recombinant antibody production systems and their applicability across various fields.

ABSTRACT P/Q‐type voltage‐dependent calcium channel CACNA1A mutations cause dominantly inherited migraine, episodic ataxia, and cerebellar atrophy in humans and cause recessively inherited ataxia, episodic dyskinesia, cerebellar atrophy, and absence epilepsy in mice. The basis of these species differences and the disease mechanism(s) are not understood. To address this question and to identify required P/Q function in vivo , we created a germline Cacna1a null mutation (designated Cacna1a Fcrtm1 ) by gene targeting. Null mice develop dystonia and late‐onset cerebellar degeneration in a specific pattern. This indicates a requirement for P/Q function for survival in a subset of cerebellar neurons. Homozygous null mice completely lack P/Q‐type channel activity, and they also lack ω‐CTx‐MVIIC receptors, indicating that a single gene encodes P/Q channel activity. An increase of L‐and N‐type current densities is detected in P/Q‐null granule cells. Heterozygous Cacna1a Fcrtm1 /+ mice are phenotypically normal, despite having a 50% reduction in current density, indicating that reduced current density is not itself sufficient to cause the pathophysiology of spontaneous mouse mutants with ataxia and seizures.