A Hybrid Biomaterial-biological Vector for Antigen Presenting Cell Gene Delivery

描述(由申请人提供)：拟议的R03试点研究将把两个传统的基因传递载体组合成一种新的杂交设备，有可能超过任何一个原始载体的基因传递效率。生物材料因其固有的生物相容性和可调节的特性而成为促进基因传递的主要载体，可用于影响细胞传递机制。最近，细菌载体也被用于基因传递，并提供了一组正交的生物工程参数，以进一步影响细胞基因传递过程。在这项工作中，将产生一种结合了两个单独载体的最佳特征的混合生物材料-细菌装置。更具体地说，以前使用生物材料或细菌载体进行靶向抗原提呈细胞基因传递的研究现在将结合起来，以努力提高对这些特定细胞的基因传递效率。新的生物材料-生物混合载体带来的基因传递的改善将使这项技术成为创新。更重要的是，混合设备将为工程设计提供一个全新的平台，其中包括聚合物化学和分子生物学等不同的工具，以进一步修改和提高载体的效力。这将是未来拨款申请的一个关键主题，通过塔夫茨工程学院和医学院之间建立的联系，促进新设备的应用，作为预防传染病和癌症的基因疫苗。 与公共健康相关：Success将提供两个与健康相关的成果：1)一种全新的基因传递装置，具有生物和生物材料工程工具，可用于未来的优化；2)一种广泛的平台技术，致力于新的疾病模型和更先进的治疗应用。

DESCRIPTION (provided by applicant): The proposed R03 pilot study will combine two traditional gene delivery vectors into a novel hybrid device with potential to surpass the gene delivery efficacy of either original vector. Biomaterials have been a primary vehicle to facilitate gene delivery due to their inherent biocompatibility and adjustable properties available to influence cellular delivery mechanisms. More recently, bacterial vectors have also been used for gene delivery and provide an orthogonal set of biological engineering parameters to further influence the cellular gene delivery process. In this work, a hybrid biomaterial-bacterial device will be generated that combines the best features of both individual vectors. More specifically, previous studies using either biomaterial or bacterial vectors for targeted antigen presenting cell gene delivery will now be combined in an effort to boost gene delivery efficacy to these particular cells. Improved gene delivery as a result of the new hybrid biomaterial- biological vectors will establish the technology as innovative. More importantly, the hybrid devices will provide a completely new platform for engineering design that includes disparate tools such as polymer chemistry and molecular biology to further modify and technically advance the potency of the vectors. This will be a key theme of future grant submissions as will be the application of the new devices, facilitated through established connections between Tufts' Schools of Engineering and Medicine, as genetic vaccines against infectious disease and cancer. PUBLIC HEALTH RELEVANCE: Success will provide two health-related outcomes: 1) a completely new gene delivery device with biological and biomaterial engineering tools available for future optimization and 2) a broad platform technology to be dedicated to new disease models and more advanced therapeutic applications.