STTR Phase I: Protease-based purification of recombinant human matrix metalloproteases

这一小型企业技术转让(STTR)第一阶段项目的更广泛影响是一项能够改善对许多疾病的研究的技术。这个STTR项目将开发人类基质金属蛋白酶(MMPs)，这是一种能降解许多生物分子的酶，包括人体中含量最丰富的结构蛋白-胶原。MMPs在许多正常和病理过程中都是至关重要的，例如肿瘤生长。然而，MMPs的生产成本很高，研究人员需要可靠的来源，以充分表征人类MMPs，以便研究人员能够在基础科学和医学应用方面进行高质量、可靠的实验。此外，该项目还可能影响其他使用酶的领域，如食品工业、可再生能源和人类健康。拟议的项目将使在大肠杆菌中生产的廉价重组人MMPs商业化。MMPs降解和调节细胞外基质(ECM)的各种结构成分，影响实体肿瘤的转移等病理过程，而转移的发生离不开MMPs介导的胶原蛋白降解。重组MMPs可以支持这一研究。这一STTR项目将推动基于蛋白酶的蛋白质纯化的发展，使快速和低成本的纯化成为可能。技术研发任务包括为MMP制定技术评估。技术评估将包含MMPs在不同溶液条件下的纯度、特性、浓度和活性的原始和精选数据。本项目将研究MMPs作为抗生物被膜和抗凝血剂的发展，超越传统的胶原降解研究领域。用来获得MMPs的基于酶的方法也可以用于纯化其他蛋白质。MMPs还在从组织样本和涉及异常胶原沉积的疾病中分离细胞的组织成分的广谱降解方面具有生物技术应用。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact of this Small Business Technology Transfer (STTR) Phase I project is an enabling technology to improve research into many diseases. This STTR project will develop human matrix metalloprotease (MMPs), a class of enzymes that degrade many biomolecules including collagen, the most abundant structural protein in the human body. MMPs are critical for numerous normal and pathological processes, such as tumor growth. However, MMPs are expensive to produce, and researchers need a reliable source of well-characterized human MMPs so that researchers can pursue high quality, reliable experiments on basic science and medical applications. Furthermore, this project can impact other fields that use enzymes, such as the food industry, renewable energy, and human health.The proposed project will commercialize inexpensive recombinant human MMPs produced in E. coli. MMPs degrade and regulate various structural components of the extracellular matrix (ECM), impacting pathologies such as metastasis of solid tumors, which cannot occur without MMP-mediated degradation of collagens. Recombinant MMPs can support this research. This STTR project will advance development of protease-based protein purification without chromatography, enabling rapid and low-cost purification. The technical R&D tasks include developing technical assessments for MMPs. The technical assessments will contain raw and curated data for purity, identity, concentration, and activity of MMPs at different solution conditions. This project will investigate development of MMPs as anti-biofilm and anti-clot agents beyond the traditional collagen degradation field of research. The protease-based method used to obtain MMPs can be used to purify other proteins as well. MMPs also have biotechnological applications in broad-spectrum degradation of tissue components for cell isolation from tissue samples and diseases involving aberrant collagen depositions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.