“With the new technology, we caused cancer cells to produce the toxic protein that eventually killed them,” the researchers said.

By World Israel News Staff

For the first time ever, researchers encoded a toxin produced by bacteria into mRNA (messenger RNA) molecules and delivered these particles directly to cancer cells, causing the cells to produce the toxin – which eventually killed them with a success rate of 50%, Tel Aviv University (TAU) announced in a press release on Sunday.

The groundbreaking study was led by PhD student Yasmin Granot-Matok and Prof. Dan Peer, a pioneer in the development of RNA therapeutics and Head of the Nanomedicine Laboratory at the Shmunis School of Biomedicine and Cancer Research, also serving as TAU’s VP R&D. The study’s results were published in Theranostics.

研究人员说:“利用新技术,我们使癌细胞产生有毒蛋白质,最终杀死它们。”

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研究人员有史以来第一次将细菌产生的毒素编码成 mRNA(信使 RNA)分子,并将这些颗粒直接传递给癌细胞,导致细胞产生毒素,最终杀死癌细胞,成功率达 50%,Tel阿维夫大学(TAU)在周日的新闻稿中宣布。

这项开创性的研究由博士生 Yasmin Granot-Matok 和 Dan Peer 教授领导。Dan Peer 教授是 RNA 疗法开发的先驱,也是 Shmunis 生物医学和癌症研究学院纳米医学实验室的负责人,同时担任 TAU 的研发副总裁。该研究结果发表在《Theranostics》上。

“Many bacteria secrete toxins. The most famous of these is probably the botulinum toxin injected in Botox treatments. Another classic treatment technique is chemotherapy, involving the delivery of small molecules through the bloodstream to effectively kill cancer cells,” Peer explains.

“However, chemotherapy has a major downside: it is not selective, and also kills healthy cells. Our idea was to deliver safe mRNA molecules encoded for a bacterial toxin directly to the cancer cells – inducing these cells to actually produce the toxic protein that would later kill them. It’s like placing a Trojan horse inside the cancer cell.”

“许多细菌会分泌毒素。其中最著名的可能是肉毒杆菌毒素治疗中注射的肉毒杆菌毒素。另一种经典的治疗技术是化疗,涉及通过血流输送小分子以有效杀死癌细胞,”Peer 解释道。

“然而,化疗有一个主要缺点:它没有选择性,而且还会杀死健康细胞。我们的想法是将编码细菌毒素的安全 mRNA 分子直接传递给癌细胞,诱导这些细胞真正产生有毒蛋白质,随后杀死它们。这就像在癌细胞内放置了特洛伊木马。”

First, the research team encoded the genetic information of the toxic protein produced by bacteria of the pseudomonas family into mRNA molecules (resembling the procedure in which genetic info of COVID-19’s ‘spike’ protein was encoded into mRNA molecules to create the vaccine). The mRNA molecules were then packaged in lipid nanoparticles developed in Peer’s laboratory and coated with antibodies – to make sure that the instructions for producing the toxin would reach their target, the cancer cells.

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The particles were injected into the tumors of animal models with melanoma skin cancer. After a single injection, 44-60% of the cancer cells vanished.

首先,研究小组将假单胞菌家族细菌产生的有毒蛋白的遗传信息编码到mRNA分子中(类似于将COVID-19的“刺突”蛋白的遗传信息编码到mRNA分子中以制造疫苗的过程)。然后,mRNA 分子被包装在 Peer 实验室开发的脂质纳米颗粒中,并涂上抗体,以确保产生毒素的指令能够到达目标——癌细胞。

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这些颗粒被注射到患有黑色素瘤皮肤癌的动物模型的肿瘤中。单次注射后,44-60% 的癌细胞消失了。
“In our study, the cancer cell produced the toxic protein that eventually killed it,” says Peer. “We used pseudomonas bacteria and the melanoma cancer, but this was only a matter of convenience. Many anaerobic bacteria, especially those that live in the ground, secrete toxins, and most of these toxins can probably be used with our method.

Tel Aviv University Prof. Dan Peer
Tel Aviv University Prof. Dan Peer (TAU)

“This is our ‘recipe’, and we know how to deliver it directly to the target cells with our nanoparticles. When the cancer cell reads the ‘recipe’ at the other end it starts to produce the toxin as if it were the bacteria itself and this self-produced toxin eventually kills it.
“在我们的研究中,癌细胞产生了最终杀死它的有毒蛋白质,”皮尔说。 “我们使用了假单胞菌和黑色素瘤,但这只是为了方便。许多厌氧细菌,尤其是那些生活在地下的厌氧细菌,会分泌毒素,而这些毒素中的大多数可能都可以用我们的方法来使用。

特拉维夫大学 Dan Peer 教授
特拉维夫大学 Dan Peer 教授 (TAU)

“这是我们的‘配方’,我们知道如何用我们的纳米颗粒将其直接递送至靶细胞。当癌细胞读取另一端的“食谱”时,它开始产生毒素,就好像细菌本身一样,这种自身产生的毒素最终会杀死它。
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“Thus, with a simple injection to the tumor bed, we can cause cancer cells to ‘commit suicide’, without damaging healthy cells,” he said. “Moreover, cancer cells cannot develop resistance to our technology as often happens with chemotherapy – because we can always use a different natural toxin.”

Other contributors to the study included: Dr. Assaf Ezra, Dr. Srinivas Ramishetti, Dr. Preeti Sharma Dr. Gonna Somu Naidu and Prof. Itai Benhar, Head of the Antibody Engineering Lab at the Shmunis School of Biomedicine and Cancer Research at TAU. The study was funded by the Shmunis Family Foundation for Biomedicine and Cancer Research.
“因此,通过简单地向肿瘤床注射,我们就可以导致癌细胞‘自杀’,而不会损害健康细胞,”他说。 “此外,癌细胞不会像化疗时经常发生的那样对我们的技术产生耐药性——因为我们总是可以使用不同的天然毒素。”

该研究的其他贡献者包括:Assaf Ezra 博士、Srinivas Ramishetti 博士、Preeti Sharma 博士、Gonna Somu Naidu 博士和特拉维夫大学 Shmunis 生物医学和癌症研究学院抗体工程实验室负责人 Itai Benhar 教授。该研究由施穆尼斯家族生物医学和癌症研究基金会资助。