eSynthesis - an automated platform technology for rapid, high-throughput and clonal cell-free synthetic DNA synthesis

eSynthesis - 一种自动化平台技术，用于快速、高通量和克隆无细胞合成 DNA 合成

• 批准号: 10075886
• 金额: $ 5.54万
• 依托单位: APALOS LTD
• 依托单位国家: 英国
• 项目类别: Grant for R&D
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=10075886
• 关键词: eSynthesis; automated; platform; technology; rapid

_The market pull_Synthesis of custom DNA and proteins is vital for biotechnology innovation across a wide range of industries and demand for both is accelerating. Next-generation sequencing has produced a vast library of natural DNA code that can be harnessed and customised for the engineering of new and improved products, from therapeutic proteins to bio-industrial enzymes. But the UK lacks a domestic DNA synthesis service with the capacity to deliver custom products with the complexity, speed and variant-throughput necessary for R&D pipelines to iterate effectively._Why cell-free?_We share a critical bottleneck with many of our customers - the loss of time, throughput, resource and purity as a result of traditional bacterial cloning. Cell-free approaches enable automation, process miniaturisation and high-throughput, improving the scale at which DNA/protein variants can be synthesised and screened by orders of magnitude. Cell-free also enables production of molecules toxic to cells or exhibiting new-to-nature biochemistries._Our innovation_We will build the eSynthesis platform, exploiting state-of-the-art enzymatic DNA synthesis (EDS) by developing technology for cell-free clonal amplification of assembled parts. We are among the first UK service providers to utilise EDS and we are primed to exploit the superior length and error-rate of EDS oligonucleotides. We aim to reproduce what cells do well, clonal replication of DNA, in an automatable cell-free process that delivers speed, cost and throughput benefits. Our mission is to lead a new paradigm shift in synthetic biology R&D defined by complete control of molecular context.Our areas of innovation will include: (a) novel plasmid DNA amplification technology that avoids cell-based propagation, (b) an automated, high-throughput and DNA synthesis platform, and (c) generation of DNA variant libraries for suitable for screening applications._Impacts_Our eSynthesis platform will enable us to: (a) deliver complex/difficult to replicate, highly-purified and application-agnostic custom DNA products quicker and at lower cost than established competitors, and (b) leverage our existing downstream cell-free protein synthesis service to screen libraries of expressed variants at an otherwise unfeasibly high throughput. Our value proposition to customers will be the ability to iterate faster through discovery and product optimisation pipelines.

市场拉动-定制DNA和蛋白质的合成对广泛行业的生物技术创新至关重要，对两者的需求都在加速。下一代测序已经产生了一个庞大的天然DNA密码库，可以利用和定制这些密码库来设计新的和改进的产品，从治疗性蛋白质到生物工业酶。但英国缺乏国内DNA合成服务，无法提供具有研发管道有效迭代所需的复杂性、速度和可变吞吐量的定制产品。_为什么不使用细胞？_我们与许多客户共享一个关键瓶颈--传统细菌克隆造成的时间、产量、资源和纯度的损失。无细胞方法使自动化、过程小型化和高通量成为可能，从而提高了合成和筛选DNA/蛋白质变体的规模。无细胞还可以生产对细胞有毒的分子或表现出全新的生物化学。_我们的创新_我们将建立电子合成平台，通过开发组装部件的无细胞克隆放大技术来利用最先进的酶DNA合成(EDS)。我们是首批使用EDS的英国服务提供商之一，我们已经准备好利用EDS寡核苷酸的优越长度和错误率。我们的目标是复制细胞做得好的东西，DNA的克隆复制，在一个自动化的无细胞过程中，提供速度、成本和产量优势。我们的使命是在合成生物学研发中引领一场由完全控制分子环境定义的新范式转变。我们的创新领域将包括：(A)避免基于细胞的繁殖的新型质粒DNA放大技术，(B)自动化、高通量和DNA合成平台，以及(C)适合筛选应用的DNA变异库的生成。_Impact_我们的电子合成平台将使我们能够：(A)比现有竞争对手更快、更低成本地提供复杂/难以复制、高度纯化和与应用无关的定制DNA产品，以及(B)利用我们现有的下游无细胞蛋白质合成服务，以不可行的高通量筛选表达变体的文库。我们对客户的价值主张将是能够通过发现和产品优化管道更快地迭代。