Pah1p promotes lipid droplet assembly independent of its role in triacylglycerol synthesis.
Seipin is a transmembrane protein that resides in the endoplasmic reticulum and concentrates at junctions between the ER and cytosolic lipid droplets. Mutations in the human seipin gene, including the missense mutation A212P, lead to congenital generalized lipodystrophy (CGL), characterized by the lack of normal adipose tissue and accumulation of fat in liver and muscles. In both yeast and CGL patient fibroblasts, seipin is required for normal lipid droplet morphology; in its absence droplets appear to bud abnormally from the ER. Here we report the first purification and physical characterization of seipin. Yeast seipin is in a large discrete protein complex. Affinity purification demonstrated that seipin is the main if not exclusive protein in the complex. Detergent sucrose gradients in H2O, and D2O and gel filtration were used to determine the size of the seipin complex and account for detergent binding. Both seipin-myc13 (seipin fused to 13 tandem copies of the myc epitope) expressed from the endogenous promoter and overexpressed seipin-mCherry form ~500 kDa proteins consisting of about 9 copies of seipin. The yeast orthologue of the human A212P allele forms only smaller complexes and is unstable; we hypothesize that this accounts for its null phenotype in humans. Seipin appears as a toroid by negative staining electron microscopy. We speculate that seipin plays at least a structural role in organizing droplets or in communication between droplets and ER.
Ever since relevant bioengineering technologies have sufficiently matured to the platformizable commercialization stage, a slew of money has flocked to the cell and gene therapy market over the last few years, resulting in an abundance of clinical studies in the field. Newer modalities have brought up a string of regulatory and legislative tasks, such as developing guidelines and legislative rules to systematically regulate newer pharmaceutical products. Accordingly, another layer of legislation and guidelines tailored for cell and gene therapies has been introduced and is expected to evolve on par with technological progress. Furthermore, authorities have shifted to pricing and reimbursement policies that can share risks for cost and outcome among stakeholders altogether, such as developers and the government, while expanding the accessibility of patients to innovative cell and gene therapies. This review attempts to capture the salient regulatory features of the cell and gene therapy market in the context of South Korea and the European Union and points out where two sovereign entities currently stand on each policy element and how each tackles regulatory challenges. We can observe the converging trend where regulatory, pricing and reimbursement rules of adjoining countries in the supranational union or member countries of a consortium are getting more aligned. Evidently, concerted efforts to share regulatory science knowledge and embrace reference pricing have played their parts. The authors argue that policy priorities should be placed on initiatives to harmonize with other medical authorities to better the rights of patients and clear out the uncertainties of developers, ultimately to share and advance regulatory science and layout forward-looking policies at opportune times.
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