Scaling up bacterial minicell production

描述(申请人提供)：“扩大细菌微型细胞的生产”该项目的重点是扩大细菌微型细胞的生产，以满足任何基于Vaxiion微型细胞产品的预期市场需求。我们建议使用一种经过优化的单一遗传方法来构建一组来自大肠杆菌、沙门氏菌、志贺氏菌和弯曲杆菌的微型细胞生产菌株，以最大限度地提高整个小组的微型细胞产量。这项建议的第一个目的是准确地确定高度保守的ftsQAZ中哪些基因需要过度表达才能获得最大的微细胞产量。这项提议的第二个目的是，使用相同的程序和材料，将先前工作中确定的基因组合引入到所列出的每一种生物的染色体上。然后，这些菌株将在小规模(&lt；10L)发酵的优化生长条件下进行生产能力测试，并在实验基础上与最终将处理所有未来大规模(&lt；100L)生产的CMO一起运行。与公共健康相关：“扩大细菌微细胞生产”Vaxiion治疗公司专注于将几种基于细菌微细胞的专利产品推向市场。这里没有详细说明，Vaxiion已将细菌微细胞平台技术定位为用于疫苗开发、癌症治疗药物的靶向输送以及体内早期靶向肿瘤生物成像。虽然这三个项目都在各自的临床前开发阶段取得了进展，但仍然存在一个至关重要的问题，即所有这些产品都有共同之处，如果要将微型细胞推向市场，就必须解决这些问题。问题是Vaxiion扩大生产和提纯的能力，以满足对所有这些产品的预计需求。如果这笔资金用于第一阶段SBIR赠款提案，将用于解决生产问题，而第二阶段将主要专注于大规模生产和提纯。

DESCRIPTION (provided by applicant): "Scaling up bacterial minicell production" This project is focused around scaling up bacterial minicell production to meet projected market demands of any of Vaxiion minicell-based products. We propose to construct a panel of minicell producing strains from E. coli, Salmonella spp, Shigella spp, and Campylobacter using a single genetic approach that has been optimized to maximize minicell productions across the panel. The first aim of this proposal is to identify exactly which genes within the highly conserved ftsQAZ need to be over expressed to obtain maximum minicell production. The second aim of this proposal is to introduce, using the same procedure and materials in parallel, the gene combination identified in the previous effort on to the chromosome of each of the organisms listed. These strains will then be tested for production capacity in growth conditions optimized in small scale (<10L) fermentation runs on an experimental basis in conjunction with a CMO that will eventually be handling all future large scale (<100L) production. PUBLIC HEALTH RELEVANCE: "Scaling up bacterial minicell production" Vaxiion Therapeutics, Inc. Is focused on brining several proprietary bacterial minicell-based products to market. Without going into much detail here, Vaxiion has positioned the bacterial minicell platform technology to be used in vaccine development, targeted delivery of cancer therapeutics, and early stage in vivo targeted tumor bio-imaging. While all three programs are making progress in their respective stages of preclinical development, there remains one vital issue that all of these would be products have in common that must be addressed if minicells are ever to be brought to market. The issue is the ability of Vaxiion to scale up both production and purification to meet projected demand for all of these products. The funds, if awarded for this Phase I SBIR grant proposal will be used to address production, while Phase II would focus primarily on large scale production and purification.