权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Engineering and intracellular delivery of recombinant antibodies

重组抗体的工程设计和细胞内递送

基本信息

批准号：
1807415
负责人：
James Van Deventer
金额：
$ 47.32万
依托单位：
Tufts University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2022-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1807415&HistoricalAwards=false
关键词：
Engineering intracellular delivery recombinant antibodies

项目摘要

AbstractsNontechnical Abstract:Antibodies are used as key tools for conducting biological research and are used as therapeutics for cancer, arthritis, and other conditions. While antibodies can be engineered to precisely target nearly any biological process, they cannot access the insides of cells, limiting their applications. A general strategy for introducing antibodies into cells would enable many new studies of how cells function and would also enable new therapies to be developed. This proposal will examine the key factors that will enable the introduction of antibodies into cells using a drug delivery strategy based on very small particles called nanoparticles. Because antibodies share a large number of common features, the specific work of this project is anticipated to lead directly to very broad applications in understanding how cells work and, in the long term, how to target processes that lead to disease initiation and progression. This project will support rigorous research training for graduate and undergraduate students at Tufts University. In addition, an expanded summer research program will provide opportunities for introducing area high school students to key concepts in the modern biotechnology industry, a rapidly growing portion of the local economy.Technical Abstract:Antibodies are key tools used in biological research that can be engineered to precisely interfere with individual signaling events, but intracellular applications of antibodies remain limited because of ongoing delivery challenges. This project will establish a general strategy for delivering antibodies intracellularly with the ultimate goal of targeted therapies for cancer and other diseases. To realize this approach, specific work to be conducted in this proposal will enable the elucidation of the molecular features that dictate effective antibody nanoparticle formulation, intracellular delivery, and interference with cell signaling. Because antibodies can be engineered to disrupt virtually any process of interest, this project will facilitate the establishment of general strategies for interfering with intracellular processes without the need for genetically modifying target cells. Robust strategies for intracellular antibody delivery have the potential to enable rapid exploration of therapeutic targets in a variety of diseases, including those targets traditionally viewed as "undruggable". The proposed work will train undergraduate, and graduate students in conducting rigorous scientific research in the areas of protein engineering and nanobiotechnology. In addition, expanding an existing summer research program to include a three-week Tufts Summer Camp for Protein Engineering and Nanomedicine (TUSC-PEN) will provide opportunities for introducing area high school students to key concepts in crucially important areas of the modern biotechnology industry.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

摘要：抗体是进行生物学研究的关键工具，被用作治疗癌症、关节炎和其他疾病的药物。虽然抗体可以被设计成精确地针对几乎任何生物过程，但它们不能进入细胞内部，限制了它们的应用。将抗体引入细胞的一般策略将使许多关于细胞功能的新研究成为可能，也将使新的治疗方法得以开发。这一提议将研究能够利用一种基于被称为纳米颗粒的非常小的颗粒的药物递送策略将抗体引入细胞的关键因素。由于抗体具有大量的共同特征，预计该项目的具体工作将直接导致非常广泛的应用，以了解细胞如何工作，并从长远来看，如何靶向导致疾病发生和进展的过程。该项目将为塔夫茨大学的研究生和本科生提供严格的研究培训。此外，扩大的暑期研究项目将为当地高中生介绍现代生物技术产业的关键概念提供机会，生物技术产业是当地经济中快速增长的一部分。技术摘要：抗体是生物学研究中使用的关键工具，可以通过工程设计来精确干扰单个信号事件，但由于持续存在的递送挑战，抗体在细胞内的应用仍然有限。该项目将建立细胞内递送抗体的总体策略，最终目标是针对癌症和其他疾病进行靶向治疗。为了实现这一方法，本提案中进行的具体工作将能够阐明决定有效抗体纳米颗粒配方、细胞内递送和细胞信号干扰的分子特征。由于抗体可以被设计来破坏几乎任何感兴趣的过程，因此该项目将有助于建立干扰细胞内过程的一般策略，而无需对靶细胞进行基因修饰。细胞内抗体递送的稳健策略有可能使快速探索各种疾病的治疗靶点成为可能，包括那些传统上被视为“不可药物”的靶点。这项工作将培养本科生和研究生在蛋白质工程和纳米生物技术领域进行严谨的科学研究。此外，扩大现有的暑期研究项目，包括为期三周的蛋白质工程和纳米医学塔夫茨夏令营（TUSC-PEN），将为当地高中生介绍现代生物技术产业至关重要领域的关键概念提供机会。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。