Bioengineering a Novel Therapeutic Transporter that Crosses the Blood Brain Barrier to Treat Brain Disorders

虽然脑血屏障(Bbb)是保护大脑的重要生理屏障，但它也代表着一种 治疗性交付的可形成屏障。因此，迫切需要能够注射的治疗性转运体。 静脉注射，并有效地穿过血脑屏障，将治疗剂输送到大脑[1-8]。[医]胞核 Treateutics公司率先开发了一种新的生物启发递送剂(CargocytesTM)，具有满足 这一迫切需要。Cargocell是经过生物工程处理的去核间充质基质细胞(MSCs)，它是 病变组织，如大脑，并在静脉注射后提供治疗有效载荷。行政管理。我们在这方面的大量工作 实验室表明，碳细胞具有治疗脑部疾病的潜力，因为它们很容易通过血管渗出 屏障，侵入内皮细胞基底膜，通过复杂的细胞外基质对靶组织实施化疗 在疾病中心的深处。碳细胞也可以被改造成生产、分泌和/或传递一系列强大的 脑环境中的治疗，包括细胞因子、神经营养因子、抗体、纳米抗体、RNA，甚至 小分子药物。总体而言，我们的发现表明Cargocell是一个新的突破性技术平台 最大限度地提供和生产本地生物蛋白，同时最大限度地减少全身性分布。Cargocell技术 提高疗效并减少偏离目标的毒性，这是治疗提供的“圣杯”。这样做的主要目标是 第一阶段的应用是利用已建立的脑缺血模型开发跨越血脑屏障的脑归巢细胞。 脑部受伤。

While the brain blood barrier (BBB) is an important physiological barrier that protects the brain, it is also represents a formable barrier to therapeutic delivery. Therefore, there is a critical need for therapeutic transporters that can be injected intravenously (i.v.), and effectively traverse the BBB and deliver therapeutic agents to the brain [1-8]. Cytonus Therapeutics has pioneered the development of a new bioinspired delivery agent (CargocytesTM) with potential to meet this critical need. Cargocytes are bioengineered enucleated mesenchymal stromal cells (MSCs) that specifically home to diseased tissues such as the brain and deliver therapeutic payloads following i.v. administration. Substantial work in our laboratory indicates that Cargocytes have potential to treat brain disorders as they readily extravasate through vascular barriers, invade endothelial basement membranes, and chemotax though complex extracellular matrices to target tissues deep within disease foci. Cargocytes can also be engineered to produce, secrete, and/or deliver a range of powerful therapeutics within the brain milieu including cytokines, neurotrophic factors, antibodies, nanobodies, RNAs, and even small molecule drugs. Overall, our findings demonstrate that Cargocytes are a new breakthrough technology platform for maximum local bioprotein delivery and production while minimizing systemic distribution. Cargocyte technology improves efficacy and reduces off-target toxicity, the “holy grail” of therapeutic delivery. The primary objective of this phase I application is to develop brain homing Cargocytes that cross the BBB using an established model of ischemic brain injury.