Controlled Cell Membrane Disruption:Gene Transfection

一个细胞群体可以通过打破细胞质膜来适应外源分子的摄取。这允许将所需的基因分子掺入靶细胞。细胞膜的过度破裂将导致细胞种群活力的不良损失，因为所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。这个SBIR第一阶段的应用程序建议开发一种微栅破坏，当微栅生效时，预计给定种群中的所有细胞都会受到破坏。适当程度的膜破裂将维持细胞群体的活力，并实现对所需外源分子的感受性(S)。微栅系统的概念简单、经济，是一种理想的基因转染设备。重点将放在微栅的微制造、微栅的详细结构和栅元件的表面化学上。这项研究的第二阶段将集中于评估用于基因治疗应用的微栅系统的几个原型。建议的商业应用：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她的细胞群体的生存能力。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.