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

这个小企业创新研究（SBIR）第一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，可以重新定义蛋白质构建模块的性质，并成为美国创新和经济增长的主要驱动力。通过改造新的微生物及其相关的细胞机制，该技术可以将多种非天然成分掺入蛋白质中，从而创造出一类新的生物材料，用于治疗开发，生物材料开发和其他生物医学研究领域。这些新设计的蛋白质可以被专门改造以添加所需的功能，从而导致生物医学领域新产品的智能设计。这个第一阶段项目旨在解决该领域当前方法的局限性，创建一个能够整合合成起始材料的综合平台，并表征这些修饰如何影响微生物细胞生长和适应性。这些进展可能为设计和生产具有增强功效和功能的下一代产品建立新的范例，推动新疗法和材料的开发，以实现变革性的社会，医疗和经济效益。拟议的项目将解决在开发合成生物聚合物的综合平台方面的主要可行性挑战，独特的合成化学赋予新的化学和生物物理功能。扩展遗传密码的努力已经表明，天然翻译系统能够选择性地掺入广泛的合成氨基酸（sAA）。然而，几个障碍已经基本上限制了该领域的只有一个或几个情况下，网站特异性掺入的sAA。其中包括：改变核糖体序列的生物学限制，sAA掺入的正交翻译系统的低效率，以及将生物聚合物合成限制为标记和修饰方法或简单蛋白质修饰的不可用的开放密码子。该项目旨在通过将含有工程翻译机制的基因组重新编码生物体与Ribo-T相结合，以解决将这种创新推向市场的这些挑战，从而能够生产具有合成单体的合成生物聚合物。此外，该项目旨在建立将两种不同的sAA编码到单个聚合物中的技术能力。这些第一阶段的目标将共同推动生物材料平台的发展，以生产具有多种合成化学成分的合成生物聚合物，从而降低通往新型聚合物生物制品的风险。该奖项反映了NSF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。

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.