Bacterial Living Therapeutics with Engineered Protein Secretion Circuits to Eliminate Breast Cancer Cells

IF 3.7 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

ACS Synthetic Biology Pub Date : 2024-10-05 DOI:10.1021/acssynbio.3c0072310.1021/acssynbio.3c00723

Gozeel Binte Shahid, Recep Erdem Ahan, Julian Ostaku and Urartu Ozgur Safak Seker*,

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Abstract

Cancer therapy can be limited by potential side effects, and bacteria-based living cancer therapeutics have gained scientific interest in recent years. However, the full potential of bacteria as therapeutics has yet to be explored due to engineering challenges. In this study, we present a bacterial device designed to specifically target and eliminate breast cancer cells. We have engineered Escherichia coli (E. coli) to bind to HER2 receptors on breast cancer cells while also secreting a toxin, HlyE, which is a pore-forming protein. The binding of E. coli to HER2 is facilitated by a nanobody expressed on the bacteria’s surface via the Ag43 autotransporter protein system. Our findings demonstrate that the nanobody efficiently binds to HER2+ cells in vitro, and we have utilized the YebF secretion tag to secrete HlyE and kill the target cancer cells. Overall, our results highlight the potential of our engineered bacteria as an innovative strategy for breast cancer treatment.

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利用工程化蛋白质分泌回路消灭乳腺癌细胞的细菌活体疗法

癌症治疗可能会受到潜在副作用的限制，而基于细菌的活体癌症疗法近年来受到了科学界的关注。然而，由于工程方面的挑战，细菌作为治疗剂的全部潜力还有待开发。在本研究中，我们介绍了一种专门针对并消除乳腺癌细胞的细菌装置。我们改造了大肠杆菌（E. coli），使其与乳腺癌细胞上的 HER2 受体结合，同时分泌一种毒素 HlyE，这是一种孔形成蛋白。大肠杆菌与 HER2 的结合是由细菌表面表达的纳米抗体通过 Ag43 自转运蛋白系统促成的。我们的研究结果表明，纳米抗体能在体外有效地与 HER2+ 细胞结合，我们还利用 YebF 分泌标签分泌 HlyE 并杀死目标癌细胞。总之，我们的研究结果凸显了我们的工程细菌作为乳腺癌治疗创新策略的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Synthetic Biology 生物-

CiteScore

8.00

自引率

10.60%

发文量

380

审稿时长

6-12 weeks

期刊介绍： The journal is particularly interested in studies on the design and synthesis of new genetic circuits and gene products; computational methods in the design of systems; and integrative applied approaches to understanding disease and metabolism. Topics may include, but are not limited to: Design and optimization of genetic systems Genetic circuit design and their principles for their organization into programs Computational methods to aid the design of genetic systems Experimental methods to quantify genetic parts, circuits, and metabolic fluxes Genetic parts libraries: their creation, analysis, and ontological representation Protein engineering including computational design Metabolic engineering and cellular manufacturing, including biomass conversion Natural product access, engineering, and production Creative and innovative applications of cellular programming Medical applications, tissue engineering, and the programming of therapeutic cells Minimal cell design and construction Genomics and genome replacement strategies Viral engineering Automated and robotic assembly platforms for synthetic biology DNA synthesis methodologies Metagenomics and synthetic metagenomic analysis Bioinformatics applied to gene discovery, chemoinformatics, and pathway construction Gene optimization Methods for genome-scale measurements of transcription and metabolomics Systems biology and methods to integrate multiple data sources in vitro and cell-free synthetic biology and molecular programming Nucleic acid engineering.