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工程化病毒样颗粒实现有效的体内递送治疗性蛋白质
作者:小柯机器人 发布时间:2022/1/14 16:52:02

美国哈佛大学刘如谦研究小组开发出工程化病毒样颗粒实现有效的体内递送治疗性蛋白质。2022年1月11日,《细胞》杂志在线发表了这项成果。

研究人员报道了工程化无DNA病毒样颗粒(eVLP)的开发和应用,它能有效地包装和传递碱基编辑或Cas9核糖核蛋白。通过工程化的VLP来克服货物包装、释放和定位的瓶颈,研究人员开发了第四代eVLP,并在几种主要的小鼠和人类细胞类型中介导了高效的碱基编辑。在eVLP中使用不同的糖蛋白会改变它们的细胞趋向性。

单次向小鼠注射eVLP支持多个组织中治疗水平的碱基编辑,在63%的肝脏编辑后,血清Pcsk9水平降低78%,并部分恢复了遗传性失明小鼠模型的视觉功能。eVLP的体外和体内脱靶编辑几乎没有被发现,这是对AAV或质粒传递的改进。这些结果确立了eVLP作为治疗性大分子递送的潜在载体,并结合了病毒和非病毒递送的关键优势。

据介绍,以核糖核蛋白的形式在体内递送基因编辑剂的方法可以提供比核酸递送方法更安全的优势。

附:英文原文

Title: Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins

Author: Samagya Banskota, Aditya Raguram, Susie Suh, Samuel W. Du, Jessie R. Davis, Elliot H. Choi, Xiao Wang, Sarah C. Nielsen, Gregory A. Newby, Peyton B. Randolph, Mark J. Osborn, Kiran Musunuru, Krzysztof Palczewski, David R. Liu

Issue&Volume: 2022-01-11

Abstract: Methods to deliver gene editing agents in vivo as ribonucleoproteins could offer safety advantages over nucleic acid delivery approaches. We report the development and application of engineered DNA-free virus-like particles (eVLPs) that efficiently package and deliver base editor or Cas9 ribonucleoproteins. By engineering VLPs to overcome cargo packaging, release, and localization bottlenecks, we developed fourth-generation eVLPs that mediate efficient base editing in several primary mouse and human cell types. Using different glycoproteins in eVLPs alters their cellular tropism. Single injections of eVLPs into mice support therapeutic levels of base editing in multiple tissues, reducing serum Pcsk9 levels 78% following 63% liver editing, and partially restoring visual function in a mouse model of genetic blindness. In vitro and in vivo off-target editing from eVLPs was virtually undetected, an improvement over AAV or plasmid delivery. These results establish eVLPs as promising vehicles for therapeutic macromolecule delivery that combine key advantages of both viral and nonviral delivery.

DOI: 10.1016/j.cell.2021.12.021

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)01484-7

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/