CAMBRIDGE, Mass.--(BUSINESS WIRE)--Judo Bio, a biotechnology company pioneering oligonucleotide medicines delivered to the kidney, today announced the presentation of preclinical data that demonstrate a mechanism of uptake and trafficking of ligand-siRNA conjugates using megalin receptors to achieve targeted gene knockdown in proximal tubule epithelial cells (PTEC) of the kidney.

马萨诸塞州剑桥市（商业新闻短讯）--柔道生物是一家开创寡核苷酸药物输送到肾脏的生物技术公司，今天宣布提供临床前数据，证明使用巨蛋白受体摄取和运输配体-siRNA缀合物的机制，以实现肾脏近端小管上皮细胞（PTEC）的靶向基因敲低。

The data is being presented at Kidney Week 2024, the annual meeting of the American Society of Nephrology, taking place in San Diego, CA on October 24-27..

该数据将于10月24日至27日在加利福尼亚州圣地亚哥举行的2024年肾脏周美国肾脏病学会年会上公布。。

These data represent the capabilities of the Company’s STRIKE (Selectively Targeting RNA Into KidnEy) platform to discover ligand‑siRNA conjugates that harness the natural, endogenous process of receptor-mediated endocytosis to deliver oligonucleotide therapeutics to specific kidney cell populations.

这些数据代表了该公司的STRIDE（选择性地将RNA靶向肾脏）平台发现配体-siRNA缀合物的能力，该缀合物利用受体介导的内吞作用的天然内源性过程将寡核苷酸治疗剂递送至特定的肾细胞群。

Megalin-STRIKERs are ligand-siRNA conjugates that bind to megalin on PTECs, resulting in drug uptake to the kidney and gene silencing of the target mRNA. In its initial drug programs, Judo Bio is designing megalin-STRIKERs to silence mRNA expression of specific solute carrier (SLC) proteins, thereby inhibiting the uptake of circulating metabolites linked to systemic diseases..

Megalin-STRIKERs是与PTEC上的Megalin结合的配体-siRNA缀合物，导致药物摄取到肾脏和靶mRNA的基因沉默。在其最初的药物计划中，Judo Bio正在设计Megalin-STRIKERs以沉默特定溶质载体（SLC）蛋白的mRNA表达，从而抑制与全身性疾病相关的循环代谢物的摄取。。

“Our understanding of endocytic trafficking in kidney proximal tubule cells has advanced rapidly in recent years,” said Ora A. Weisz, PhD, an author of the poster presentation and Professor of Medicine, Cell Biology, and Clinical and Translational Science in the Division of Renal-Electrolyte at the University of Pittsburgh.

“近年来，我们对肾近端小管细胞内吞运输的理解迅速发展，”海报作者、匹兹堡大学肾脏电解质系医学、细胞生物学、临床和转化科学教授Ora A.Weisz博士说。

“This approach to harness the endocytic pathway to selectively target delivery of RNA to specific kidney cells provides an opportunity to target and silence solute carrier proteins in order to address numerous systemic diseases.”.

“这种利用内吞途径选择性靶向将RNA递送至特定肾细胞的方法提供了靶向和沉默溶质载体蛋白的机会，以解决许多全身性疾病。”。

The preclinical data presented at Kidney Week studied megalin ligand-conjugated siRNA, or megalin-STRIKERs, in a differentiated, opossum kidney PTEC cell line that recapitulates proximal tubule morphology and is functionally similar to kidneys in animals. Key findings include:

肾脏周提供的临床前数据研究了分化的负鼠肾PTEC细胞系中的巨蛋白配体偶联的siRNA或巨蛋白突变体，该细胞系概括了近端小管的形态，并且在功能上与动物的肾脏相似。主要调查结果包括：

Ligand-siRNAs were taken up by opossum kidney cells in both a time and concentration dependent manner, predominantly from the apical surface.

配体siRNA被负鼠肾细胞以时间和浓度依赖性方式摄取，主要来自顶端表面。

Uptake of ligand-siRNA conjugates was megalin dependent and achieved with different megalin ligands.

配体-siRNA缀合物的摄取是巨蛋白依赖性的，并且用不同的巨蛋白配体实现。

Megalin ligand-siRNA conjugates led to significant gene knock-down across multiple targets and was durable for up to 40 days in mice.

巨蛋白配体-siRNA缀合物导致跨多个靶标的显着基因敲低，并且在小鼠中持续长达40天。

Judo Bio’s Kidney Week poster presentation is available here on the company’s website.

柔道生物的肾脏周海报展示可在公司网站上找到。

“We are pleased to share data describing the use of megalin’s endogenous receptor-mediated endocytosis to enable gene silencing in PTECs,” said Alfica Sehgal, PhD, Chief Scientific Officer of Judo Bio. “Understanding the mechanism that leads to gene silencing directs the optimization efforts on our first megalin-STRIKERs that target SLC proteins.

柔道生物首席科学官Alfica Sehgal博士说：“我们很高兴分享数据，描述使用巨蛋白的内源性受体介导的内吞作用来实现PTEC中的基因沉默。了解导致基因沉默的机制可以指导我们针对SLC蛋白的首个巨蛋白突变体的优化工作。

Modulating function of specific SLCs is an established approach for the treatment of various systemic diseases, and an RNAi approach opens vast therapeutic opportunities because of its specificity.”.

特定SLC的调节功能是治疗各种全身性疾病的既定方法，RNAi方法因其特异性而开辟了巨大的治疗机会。”。

About Judo Bio

关于柔道生物

Judo Bio is pioneering oligonucleotide medicines delivered to the kidney, opening the way for new genetic medicines for systemic and renal diseases. With its STRIKE (Selectively Targeting RNA Into KidnEy) platform, the company is using a proprietary approach to create ligand-RNA conjugate drugs designed for receptor-mediated update by specific kidney cell types, resulting in gene silencing of disease-modifying target genes.

。凭借其STRIDE（选择性将RNA靶向肾脏）平台，该公司正在使用专有方法创建配体-RNA偶联药物，该药物旨在通过特定肾细胞类型进行受体介导的更新，从而导致疾病修饰靶基因的基因沉默。

Judo Bio’s initial pipeline programs are megalin-STRIKERs that use the megalin receptor family to selectively deliver siRNA therapeutics to the proximal tubule of the kidney to silence mRNA expression of specific solute carrier proteins (SLCs), thereby inhibiting the uptake of circulating solutes linked to systemic diseases.

柔道生物最初的管道项目是巨蛋白罢工者，他们使用巨蛋白受体家族选择性地将siRNA治疗剂递送至肾脏近端小管，以沉默特定溶质载体蛋白（SLC）的mRNA表达，从而抑制与全身疾病相关的循环溶质的摄取。

Located in Cambridge, MA, Judo Bio’s team and advisors include experts in oligonucleotide therapies and innovative drug development. For more information, visit www.judo.bio and follow us on LinkedIn..

柔道生物位于马萨诸塞州剑桥市，其团队和顾问包括寡核苷酸疗法和创新药物开发方面的专家。欲了解更多信息，请访问www.judo.bio并在LinkedIn上关注我们。。