I-Corps: Protein Transduction Domain Mimics to Revolutionize Immunology

I-Corps：蛋白质转导域模拟物将彻底改变免疫学

• 批准号: 1355761
• 负责人: Gregory Tew
• 金额: $ 5万
• 依托单位: University of Massachusetts Amherst
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1355761&HistoricalAwards=false
• 关键词: Corps; Protein; Transduction; Domain; Mimics

The proposed technology is based on the discovery of a class of polymeric protein transduction domain mimics (PTDMs) with the unique ability to intra-cellularly deliver a large variety of biomolecules (small molecules, nucleic acids, proteins and even whole, intact antibodies). Both in vitro and in vivo (with mouse models) experiments have been successfully performed demonstrating the efficacy of this technology. These molecules are synthesized via Ring-Opening Metathesis Polymerization (ROMP), which allows high fidelity over the chemical composition and structure. These PTDMs do not require covalent attached of the cargo, making this innovation applicable to various biomolecules and extremely easy to use. This innovation gives potential access to many intracellular compartments and functions thus offering new research and therapeutic opportunities.Accessibility to the human body and its highly regulated functions has always been one of the biggest challenges for biomedical sciences. The human genome and proteome projects have greatly contributed to elucidate many biological and molecular functions of the human body and to advance treatment of diseases by discovering new cellular targets. Unfortunately, this important knowledge cannot yet been fully applied because of the lack of permeability and the high selectivity of the cell membrane which makes these targets inaccessible. The delivery described in this proposal has the potential to enable many new research and application opportunities, especially, but not exclusively, in the immunology field where it will finally become possible to manipulate the so far impenetrable T-cells. T-cells play a critical role in cell-mediated immune response, for example against infections, cancer and HIV. The ability to control their activation, in a more efficient and safer way than the traditional electroporation and virus infection, will have a big societal and commercial impact.

所提出的技术是基于发现一类聚合蛋白转导结构域模拟物（PTDM），其具有在细胞内递送多种生物分子（小分子、核酸、蛋白质甚至完整的完整抗体）的独特能力。已经成功地进行了体外和体内（使用小鼠模型）实验，证明了该技术的功效。这些分子通过开环易位聚合（ROMP）合成，其允许对化学组成和结构的高保真度。这些PTDM不需要共价连接的货物，使这一创新适用于各种生物分子和非常容易使用。这一创新为许多细胞内区室和功能提供了潜在的通路，从而提供了新的研究和治疗机会。人体及其高度调节的功能的可及性一直是生物医学科学面临的最大挑战之一。人类基因组和蛋白质组计划极大地有助于阐明人体的许多生物和分子功能，并通过发现新的细胞靶点来推进疾病的治疗。不幸的是，由于细胞膜缺乏渗透性和高选择性，使得这些目标无法实现，因此这一重要知识尚未得到充分应用。该提案中描述的递送具有使许多新的研究和应用机会成为可能的潜力，特别是但不限于免疫学领域，在免疫学领域，最终将有可能操纵迄今为止无法穿透的T细胞。T细胞在细胞介导的免疫应答中发挥关键作用，例如对抗感染、癌症和HIV。以比传统的电穿孔和病毒感染更有效和更安全的方式控制它们的激活的能力将产生巨大的社会和商业影响。