ANIONIC COPOLYMER/TRIMETHYLAMINE CORE MICROCARRIER

年食物链中存在牛海绵状脑病(BSE) 欧洲和监管机构的反应，创造了一个独特的 一种新的微载体的机会，一种本身不含动物的载体 蛋白质，但将在无血清条件下发挥作用。阶段的结果 我的实验已经清楚地证明了 共聚三甲胺(TMA)微载体。细胞培养实验 在第一阶段中，包括使用MDCK的附着、传播和生长， MDBK、Vero、CEF、人二倍体成纤维细胞系和NOT细胞系 建议但在基因治疗方面具有商业意义的COS-7。以上都是 细胞系(人二倍体成纤维细胞除外)在血清- 自由条件，快速附着，迅速传播，并与收获 放松点。 第一阶段研究的总体目标是近期目标。 开发这种独特的微载体。研究的具体目标 建议包括：(L)演示五个细胞系的生长情况 我们生物反应器中TMA微载体上的升规模，(2)评估TMA 生产疫苗株病毒作为终点的微载体性能 (3)确定决定蛋白质的过程工程变量 合成，(4)评价TMA微载体作为基因载体 (5)使用TMA微载体评估产物的产生 细胞外基质蛋白与细胞外基质降解 蛋白水解酶。 建议的商业应用： 国产SoloHill微载体已找到应用 在美国动物保健业。瑞典的微载体用于 在含血清条件下的欧洲。但商业制作人 使用血清的人类生物制品很可能会变成无血清的 过程，很大程度上是由于疯牛病在欧洲的存在。研究表明， 表明这种新的TMA微载体在低成本的情况下功能很好 无血清条件下的贴壁细胞。TMA微载体可能扩大 (L)大规模细胞培养的市场应用，可能是最新的 (2)细胞治疗和(3)基因治疗应用目前处于第一阶段 临床试验。

Presence of bovine spongiform encephalopathy (BSE) in the food chain in Europe, and the reaction of regulatory agencies, has created a unique opportunity for a new microcarrier, one that is itself free of animal proteins but will function under sera-free conditions. Results of Phase I experiments have clearly demonstrated proof of principle for the copolymer trimethylamine (TMA) microcarrier. Cell culture experiments during Phase I included attachment, spreading and growth using MDCK, MDBK, VERO, CEF, human diploid fibroblast cell lines and a cell line not proposed but of commercial interest in gene therapy, COS-7. All the above cell lines (except human diploid fibroblasts) when cultured under sera- free conditions, attached quickly, spread rapidly and were harvested with ease. The overall goals of Phase Il research are aimed at the near term development of this unique microcarrier. Specific aims of the research proposed include: (l) demonstrate growth of the cell lines at the five liter scale in our bioreactor on TMA microcarriers, (2) assess TMA microcarrier performance by producing vaccine-strain viruses as endpoints (3) identify process engineering variables that determine protein syntheses, (4) assess TMA microcarriers as a support for gene transfection and (5) using TMA microcarriers assess production of extracellular matrix proteins and extracellular matrix-degrading proteolytic enzymes. PROPOSED COMMERCIAL APPLICATIONS: Domestically manufactured SoloHill microcarriers have found applications in the U. S. animal health industry. Swedish microcarriers are used in Europe under sera-containing conditions. But commercial producers of human biologicals that use serum may very likely change to sera-free processes, driven largely by the presence of BSE in Europe. Research has shown that this new TMA microcarrier functions very well with low adherent cells under sera-free conditions. TMA microcarriers may expand market usage in (l) large scale cell culture, and perhaps in the latest (2) cell therapy and (3) gene therapy applications currently in Phase I Clinical Trials.