Controlled Cell Membrane Disruption:Gene Transfection

通过使细胞的质膜破裂，可以使细胞群易于摄取外源分子。这允许将所需基因分子掺入靶细胞中。细胞膜的过度破裂将导致细胞群体的活力的不期望的损失，因为产生的破裂可能无法修复。另一方面，欠破裂可能不会产生足够程度的基因转染。该SBIR第一阶段应用提出，当微格栅有效时，预期对给定群体中的所有细胞开发微格栅破坏。膜破裂的最佳程度将维持细胞群体的活力并实现对所需外源分子的接受性。微栅系统的概念是简单和经济的，似乎是一个理想的基因转染装置。重点将放在微光栅的微细加工，微光栅的详细配置和光栅元件的表面化学。这项研究的第二阶段将集中在基因治疗应用的微光栅系统的几个原型的评估。拟议的商业应用：一旦评估和优化，本质上简单和经济的微格栅系统将简化基因加载过程，同时最大限度地利用基因和细胞群的活力。因此，预计微格栅的使用将在降低与基因治疗相关的成本方面发挥重要作用。

A cell population can be made amenable to the uptake of exogenous molecules by rupturing the plasma membranes of the cells. This allows the incorporation of the desired gene molecules into targeted cells. Over- rupturing of cell membranes will lead to undesirable loss of viability of the cell populations since the ruptures produced may be beyond repair. Under-rupturing, on the other hand, may not produce an adequate degree of gene transfection. This SBIR Phase I application proposes to develop a micrograte disruption is expected for all cells in a given population when microgrates are in effect. An optimum degree of membrane rupture will maintain the viability of a cell population and achieve receptiveness to the desired exogenous molecule(s). The micrograte system concept is simple and economical, and appears to be an ideal device for gene transfection. Emphasis will be placed on the microfabrication of microgrates, the detailed configuration of the microgrates and the surface chemistry of the grating elements. Phase II of this research will focus on the evaluation of several prototypes of micrograte systems for gene therapy applications. PROPOSED COMMERCIAL APPLICATIONS: Once evaluated and optimized, the intrinsically straightforward and economical micrograte system will simplify the gen loading process while maximizing the utilization of the genes and the viability of her cell population. It is therefore expected that the use of microgrates will play an important role in lowering the costs associated with gene therapy.