SBIR Phase I: Consolidated platform to engineer and produce novel biopolymers for improved biologics

SBIR 第一阶段：设计和生产新型生物聚合物以改进生物制剂的综合平台

• 批准号: 2233560
• 负责人: David McIntyre
• 金额: $ 27.45万
• 依托单位: PEARL BIO, INC.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2233560&HistoricalAwards=false
• 关键词: SBIR; Phase; Consolidated; platform; engineer

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is the development of a next generation biomanufacturing platform that could redefine the nature of protein building blocks and become a major driver of US innovation and economic growth. By engineering new microbial organisms and their associated cellular machinery, this technology may enable the incorporation of diverse, non-native components into proteins, creating a new class of biological materials for applications in therapeutic development, biomaterial development, and other areas of biomedical research. These newly designed proteins can be specifically engineered to add desired functionalities, leading to intelligent design of novel products in the biomedical field. This Phase I project seeks to address the limitations of current approaches in this field, creating a consolidated platform able to incorporate synthetic starting materials, and characterizing how these modifications impact microbial cell growth and fitness. These advances may establish a new paradigm for design and production of next-generation products with enhanced efficacy and functionalities, driving the development of new therapeutics and materials for transformative societal, medical, and economic benefit.The proposed project will address major feasibility challenges in the development of a consolidated platform for synthesis of synthetic biopolymers containing multiple, distinct synthetic chemistries endowing novel chemical and biophysical functionality. Efforts to expand the genetic code have shown that the natural translation system is capable of selectively incorporating a wide range of synthetic amino acids (sAAs). However, several roadblocks have substantially limited the field to only one or a few instances of site-specific incorporation of sAAs. These include: biological restrictions to altering ribosome sequence, poor efficiencies of orthogonal translation systems for sAA incorporation, and unavailable open codons that have constrained biopolymer synthesis to tag-and-modify approaches or simple protein decorations. This project seeks to address these challenges in bringing this innovation to market by combining a genomically recoded organism containing engineered translation machinery with Ribo-T to enable the production of synthetic biopolymers with synthetic monomers. Additionally, this project aims to establish the technical capabilities of encoding two distinct sAAs into a single polymer. Together, these Phase I goals will advance a biomaterials platform to produce synthetic biopolymers with multiple synthetic chemistries to de-risk a path toward novel polymer biologics.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.

这项小型企业创新研究（SBIR）I阶段项目的更广泛的影响/商业潜力是开发下一代生物制造平台，该平台可以重新定义蛋白质构件的性质，并成为美国创新和经济增长的主要驱动力。通过工程新的微生物及其相关的细胞机制，该技术可以使多种非母体成分融入蛋白质中，从而为治疗性开发，生物材料开发和其他生物医学研究领域创造了新的生物材料。这些新设计的蛋白质可以专门设计以增加所需的功能，从而在生物医学领域智能设计新型产品。该阶段I项目旨在解决该领域当前方法的局限性，创建一个能够结合合成起始材料的合并平台，并表征这些修饰如何影响微生物细胞的生长和适应性。这些进步可能会建立一个新的范式，用于设计和生产下一代产品，具有增强的功效和功能，推动开发新的治疗方法和用于变革性的社会，医疗和经济利益的材料。拟议的项目将解决与构成构成多种化学物质的合成化学化学综合构成合成的合成性化学差异的综合平台的主要可行性挑战。扩展遗传密码的努力表明，自然翻译系统能够选择性地融合多种合成氨基酸（SaaS）。但是，几个障碍大大限制了该领域，仅将特定于SaaS的现场合并的实例限制在一个或几个实例上。其中包括：改变核糖体序列的生物学限制，用于SAA掺入的正交翻译系统的效率差，以及无法使用的开放式密码子，这些密码子限制了生物聚合物合成对标记和修饰方法或简单的蛋白质装饰。该项目旨在通过将含有工程翻译机械的基因组重建生物与RIBO-T结合起来，以使这项创新成为市场的挑战，以使合成生物聚合物与合成单体的生产。此外，该项目旨在建立将两个不同的SaaS编码为单个聚合物的技术能力。这些阶段的目标将共同发展一个生物材料平台，以产生具有多种合成化学物质的合成生物聚合物，以驱散新型聚合物生物制剂的道路。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的审查标准来通过评估来通过评估来支持的。