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 the use of megalin receptors for intracellular delivery of ligand-siRNA therapeutics to the kidney to reduce expression of the target genes.

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将配体siRNA治疗剂细胞内输送到肾脏以减少靶基因的表达。

The data will be presented at the 20th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS) taking place on October 6-9 in Montreal..

这些数据将于10月6日至9日在蒙特利尔举行的寡核苷酸治疗学会（OTS）第20届年会上公布。。

STRIKE (Selectively Targeting RNA Into KidnEy) is Judo Bio’s platform to develop and discover ligand‑siRNA conjugates that harness the natural endogenous process of receptor-mediated endocytosis for uptake of oligonucleotide therapeutics to specific kidney cell populations. The data presented at OTS are from studies with ligand-siRNA conjugates that bind to megalin, a cell-surface recycling receptor that is expressed at high levels on the apical side of proximal tubule epithelial cells (PTECs), resulting in internalization and degradation of the target mRNA..

STRIKE（选择性地将RNA靶向肾脏）是柔道生物开发和发现配体-siRNA缀合物的平台，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摄取到特定的肾细胞群中。OTS上提供的数据来自与巨蛋白结合的配体-siRNA缀合物的研究，巨蛋白是一种细胞表面再循环受体，在近端小管上皮细胞（PTEC）的顶端高水平表达，导致靶mRNA的内化和降解。。

“Achieving gene silencing in the kidney has been eagerly pursued due to the central role that this organ plays in regulating normal physiology. However, selective and efficient delivery of oligonucleotide therapeutics to the kidney has been a stubborn challenge, primarily because oligonucleotides reach the kidney as a matter of course but are typically excreted without therapeutic benefit,” said Alfica Sehgal, PhD, Chief Scientific Officer of Judo Bio.

柔道生物首席科学官Alfica Sehgal博士说：“由于肾脏在调节正常生理中起着核心作用，因此迫切需要在肾脏中实现基因沉默。然而，选择性和有效地将寡核苷酸治疗剂输送到肾脏一直是一个严峻的挑战，主要是因为寡核苷酸理所当然地到达肾脏，但通常会排泄而没有治疗益处。”。

“We believe that Judo Bio has demonstrated for the first time the ability to leverage an endogenous function – in this case via megalin – for receptor-mediated transport into the cytoplasm, enabling our ligand-siRNA conjugates to achieve therapeutic gene silencing in the kidney.”.

“我们认为柔道生物首次证明了利用内源性功能（在这种情况下是通过巨蛋白）将受体介导的转运到细胞质中的能力，使我们的配体-siRNA偶联物能够在肾脏中实现治疗性基因沉默。”。

The preclinical data presented at OTS showed delivery of megalin ligand-conjugated siRNA, or megalin-STRIKERs, selectively to PTECs in the mouse kidney, and the resulting silencing of the target genes. Key findings include:

OTS上提供的临床前数据显示，巨蛋白配体偶联的siRNA或巨蛋白突变体选择性地传递给小鼠肾脏中的PTEC，并导致靶基因沉默。主要调查结果包括：

Megalin ligand-conjugated siRNA resulted in 5-30 fold increased exposure selectively in the mouse kidney compared to unconjugated naked siRNA.

与未缀合的裸siRNA相比，巨蛋白配体缀合的siRNA导致小鼠肾脏中选择性暴露增加5-30倍。

Single administration of the ligand-siRNA conjugate leads to 50-70% knockdown of target genes.

单次施用配体-siRNA缀合物导致靶基因的50-70%敲低。

Target gene knockdown with the ligand-siRNA conjugate was durable up to 4 weeks.

用配体-siRNA缀合物靶基因敲低持续长达4周。

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

柔道生物的OTS海报展示可在公司网站上找到。

“The clear and compelling data we presented for a new therapeutic approach of megalin-mediated delivery of siRNAs to the kidney opens up a host of opportunities for Judo Bio to build a pipeline of megalin-STRIKERs, initially targeting solute carrier proteins for systemic diseases,” said Dr. Sehgal. “We are excited to build on the success of our scientific progress as we bring genetic medicines to the kidney.”.

Sehgal博士说：“我们为巨蛋白介导的siRNA向肾脏传递的新治疗方法提供了清晰而令人信服的数据，这为柔道生物建立巨蛋白罢工者管道提供了许多机会，最初针对溶质载体蛋白治疗全身性疾病。”。“当我们将基因药物带到肾脏时，我们很高兴在我们科学进步的成功基础上再接再厉。”。

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.

柔道生物是向肾脏输送寡核苷酸药物的先驱，为治疗全身性和肾脏疾病的新基因药物开辟了道路。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。。