STTR Phase I: Biomanufacture of Novel Heparan Sulfate Glycosaminoglycans

STTR 第一阶段：新型硫酸乙酰肝素糖胺聚糖的生物制造

• 批准号: 1622959
• 负责人: Charles Glass
• 金额: $ 22.5万
• 依托单位: TEGA Therapeutics Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1622959&HistoricalAwards=false
• 关键词: STTR; Phase; Biomanufacture; Novel; Heparan

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) project will be to commercialize novel sugar polymers known as glycosaminoglycan (GAGs) for a variety of important medical applications. GAGs are key components in a number of important physiologic and pathophysiologic conditions (e.g., tumor angiogenesis, thrombosis); however, developing a detailed understanding of these roles, which may significantly impact human health, is challenging due to a lack of analytical techniques for glycan analysis and the absence of high quality GAG samples available for research. GAGs have precise functional roles in cell signaling cascades, which can vary depending on the particular GAG structural composition. Particular GAG compositions vary among different tissue types as well as among different developmental and physiological states. Hence, to achieve the proper functional characteristics and obtain reproducible experimental results, it is critical that GAG samples are available with consistent and defined compositions. Unfortunately, most commercially available GAG samples are from animal sources with high inherent variability and are not well characterized. The potential for contamination or adventitious agents makes the animal-derived GAG samples even less desirable for human therapeutics. This STTR Phase I project proposes to develop genetically engineered Chinese Hamster Ovary (CHO) cells producing GAGs with defined compositions. Culture conditions will be optimized to maintain GAG composition while providing product yields at a level sufficient for commercialization. A series of engineered cell lines will be produced in order to prepare GAGs with different compositions that model the different compositions and different functional characteristics found in nature. GAG samples will be characterized both structurally and functionally to provide profiles for each type of sample, which will be reliable and reproducible since the GAGs are prepared from cells grown under controlled conditions. These samples will be a valuable resource for researchers in a number of biological and medical fields. It is thought that the high quality will command premium prices. However, to help reduce costs and promote commercialization, this proposal will test growth conditions in bioreactors to increase the capacity and efficiency of production. Research using these high quality GAG samples will provide proof-of-principal for the use these GAGs in a variety of important therapeutic applications such as oncology, lipid metabolism, tissue regeneration, and hematology.

这一小型企业技术转移(STTR)项目的更广泛影响/商业潜力将是将被称为糖胺聚糖(GAGS)的新型糖聚合物商业化，用于各种重要的医疗应用。GAG是许多重要的生理和病理生理条件(如肿瘤血管生成、血栓形成)的关键成分；然而，由于缺乏分析技术和高质量的GAG样本可供研究，因此对这些可能严重影响人类健康的作用的详细了解是具有挑战性的。GAG在细胞信号级联中具有精确的功能作用，这种作用可能会因特定的GAG结构组成而异。不同的组织类型以及不同的发育和生理状态，特定的GAG组成也不同。因此，为了获得适当的功能特性并获得可重复性的实验结果，GAG样品具有一致和定义的组成是至关重要的。不幸的是，大多数商业上可获得的GAG样本来自动物来源，具有很高的内在变异性，并且没有很好的特征。潜在的污染或外来因素使动物来源的GAG样本更不适合人类治疗。这个STTRI期项目计划开发基因工程中国仓鼠卵巢(CHO)细胞，生产具有特定成分的GAG。将优化培养条件，以保持GAG的组成，同时提供足以商业化的产品产量。将生产一系列工程细胞系，以制备具有不同成分的GAG，以模拟自然界中发现的不同成分和不同功能特征。GAG样品将在结构和功能上进行表征，以提供每种类型样品的轮廓，由于GAG是从在受控条件下生长的细胞制备的，因此将是可靠和可重复性的。这些样本将成为许多生物和医学领域的研究人员的宝贵资源。人们认为，高质量的产品会卖出更高的价格。然而，为了帮助降低成本和促进商业化，这项提案将测试生物反应器的生长条件，以提高生产能力和效率。使用这些高质量的GAG样本的研究将为这些GAG在各种重要的治疗应用中的使用提供原则证明，如肿瘤学、脂质代谢、组织再生和血液学。