Nanofabricated Particles for Biolistic Delivery

描述(申请人提供)：该研究项目的目标是继续开发一系列新型纳米颗粒作为载体，通过颗粒加速方法传递各种不同类型的生物活性分子(DNA、RNA、蛋白质、多肽)和纳米颗粒传感器。这些颗粒是通过逐层技术使用纳米颗粒、聚合物和生物分子的受控组装来制造的，其中核心和后续层每一层都为最终颗粒添加特定的功能。这些纳米复合颗粒将提高目前使用的生物传递过程的效率和可靠性，并使新的生物传递应用成为可能。这包括将RNAi、反义寡核苷酸、多肽和传感器输送到活细胞和组织，用于各种生命科学研究应用，以及用于人类治疗干预。要实现的关键技术目标包括为生产纳米颗粒制定制造和工艺开发步骤，在各种模型系统应用中证明这些颗粒的增强功效，以及合成和表征一系列具有特定功能的化学上不同的颗粒。将核酸和多肽运送到感兴趣的细胞和组织的能力是基本的和必要的技术成就之一，在一定程度上一直是分子生物学、基因治疗和相关领域的基础。粒子加速方法，也被称为生物递送，是常规使用的几种递送方法之一。其中任何一种给药方法的改进都与人类健康有关，因为DNA等核酸的给药往往是医学疾病研究和开发中的一个重要步骤。我们将开发的纳米颗粒载体将显著提高生物传递过程的效率，并使其能够用于目前尚未满足需求的新型应用。

DESCRIPTION (provided by applicant): The goal of this research project is the continued development of a family of novel nanofabricated particles for use as carriers to deliver a variety of different types of bioactive molecules (DNA, RNA, proteins, peptides) and nanoparticle sensors via particle acceleration methods. The particles are fabricated using the controlled assembly of nanoparticles, polymers and biomolecules via a layer-by-layer technique where the core and subsequent layer each add specific functionality to the final particle. These nanocomposite particles will increase the efficiency and reliability of the currently used biolistic process, and enable novel biolistic delivery applications. These include the delivery of RNAi, antisense oligonucleotides, peptides, and sensors to living cells and tissues for a variety of life science research applications, and for human therapeutic interventions. The key technical objectives to be achieved include the development of manufacturing and process development steps for the production of nanofabricated particles, the documented demonstration of the enhanced efficacy of these particles in a variety of model system applications, and synthesis and characterization of a family of chemically distinct particles with specific functionality. The ability to deliver nucleic acids and polypeptides to cells and tissues of interest is one of the fundamental and required technical achievements that has, in part, been at the foundation of molecular biology, gene therapy and related fields. Particle acceleration methods, also referred to as biolistic delivery, is one of several delivery methods in routine use. Improvements to any of these delivery methods is of relevance to human health because the delivery of nucleic acids, such as DNA, is frequently an essential step in the research and development of medical diseases. The nanofabricated carrier particles we will develop will significantly improve the efficacy of the biolistic delivery process and enable its use in novel applications where currently there is an unmet need.