Process Optimization of a DNA Minivector Production System

当前项目的目标是与当前的工艺工程公司MemBio合作，优化高需求DNA微载体生产和纯化的纯化工艺。DNA微载体是线性共价闭合（LCC）分子，称为DNA微串或msDNA。在基因/细胞治疗工业中，作为用于递送遗传货物的遗传载体，具有高稳定性、功效和有效纯化的更安全的DNA载体是高需求的。该项目的成功完成将产生专有的加工知识产权，用于物理和生物化学优化msDNA生产，并使他们能够为中试规模测试做好准备。该项目的成功还将有助于通过开发可在国内和国外实施的制造工艺来加强加拿大的生物经济。迄今为止，LCC DNA与其他DNA种类的分离，无论是通过大小和拓扑结构，尚未实现超出分析水平的纯化。需要一种有效的和扩大规模的方法来产生mg规模的msDNA和其他类似的LCC DNA产物，以推动遗传医学的新发展。该提案旨在实施生物化学，遗传和物理策略，通过最具成本效益的方法纯化msDNA，并为MemBio在msDNA和其他微载体DNA生产中产生新的能力。

The objective of the current project is to collaborate with a current process engineering firm, MemBio to optimize a purification process for production and purification of a high demand DNA minivector generation. The DNA minivectors are linear covalently closed (LCC) molecules known as DNA ministrings or msDNA. Safer DNA vectors with high stability, efficacy and efficient purification are in high demand in the gene/cell therapy industry as a genetic vector for delivery of genetic cargo. Successful completion of this project will generate proprietary processing intellectual property for physically and biochemically optimizing msDNA production and allow them to get it ready for pilot-scale testing. The success of the project will also help strengthen Canadian bio-economy by developing a manufacturing process that can be implemented nationally, and abroad. To date, separation of LCC DNA from other DNA species, both by size and topology has yet to be achieved beyond analytical levels of purification. An efficient and scaled-up approach to generation of mg scale of msDNA and other similar LCC DNA products is needed to drive new developments in genetic medicine. This proposal seeks to implement biochemical, genetic and physical strategies to purify msDNA through the most cost-effective approaches available and generate novel capabilities for MemBio in msDNA and other minivector DNA production.