具有工程蛋白质分泌电路的细菌活疗法可消除乳腺癌细胞。
Bacterial Living Therapeutics with Engineered Protein Secretion Circuits to Eliminate Breast Cancer Cells.
发表日期:2024 Oct 18
作者:
Gozeel Binte Shahid, Recep Erdem Ahan, Julian Ostaku, Urartu Ozgur Safak Seker
来源:
ACS Synthetic Biology
摘要:
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引起了科学界的兴趣。然而,由于工程方面的挑战,细菌作为治疗剂的全部潜力仍有待探索。在这项研究中,我们提出了一种细菌装置,旨在专门针对和消除乳腺癌细胞。我们对大肠杆菌 (E. coli) 进行了改造,使其能够与乳腺癌细胞上的 HER2 受体结合,同时还能分泌毒素 HlyE,这是一种成孔蛋白。大肠杆菌与 HER2 的结合是通过 Ag43 自转运蛋白系统在细菌表面表达的纳米抗体来促进的。我们的研究结果表明,纳米抗体在体外能够有效地与 HER2 细胞结合,并且我们利用 YebF 分泌标签来分泌 HlyE 并杀死目标癌细胞。总的来说,我们的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。
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.