美国博德研究所刘如谦研究组开发出，用于在体内瞬时输送先导编辑核糖核蛋白复合物的工程化病毒样颗粒。2024年1月8日出版的《自然—生物技术》杂志发表了这项成果。

研究人员报告了先导编辑工程化病毒样颗粒（PE-eVLP），它能以瞬时核糖核蛋白复合物的形式递送先导编辑蛋白、先导编辑向导RNA和缺口的单向导RNA。研究人员系统地设计了v3和v3b PE-eVLP，与其之前报道的基于碱基编辑器eVLP结构的PE-eVLP构建物相比，它们在人体细胞中的编辑效率提高了65至170倍。

在两种遗传性失明的小鼠模型中，单次注射v3 PE-eVLP可在视网膜中实现治疗相关水平的素编辑、蛋白质表达恢复和部分视觉功能挽救。经过优化的PE-eVLP支持先导编辑核糖核蛋白的瞬时体内输送，并通过减少脱靶编辑和避免致癌转基因整合的可能性来提高先导编辑的潜在安全性。

据了解，先导编辑可以在活体系统中精确安装基因组置换、插入和缺失。然而，在体外和体内高效传递先导编辑元件仍然是一项挑战。

附：英文原文

Title: Engineered virus-like particles for transient delivery of prime editor ribonucleoprotein complexes in vivo

Author: An, Meirui, Raguram, Aditya, Du, Samuel W., Banskota, Samagya, Davis, Jessie R., Newby, Gregory A., Chen, Paul Z., Palczewski, Krzysztof, Liu, David R.

Issue&Volume: 2024-01-08

Abstract: Prime editing enables precise installation of genomic substitutions, insertions and deletions in living systems. Efficient in vitro and in vivo delivery of prime editing components, however, remains a challenge. Here we report prime editor engineered virus-like particles (PE-eVLPs) that deliver prime editor proteins, prime editing guide RNAs and nicking single guide RNAs as transient ribonucleoprotein complexes. We systematically engineered v3 and v3b PE-eVLPs with 65- to 170-fold higher editing efficiency in human cells compared to a PE-eVLP construct based on our previously reported base editor eVLP architecture. In two mouse models of genetic blindness, single injections of v3 PE-eVLPs resulted in therapeutically relevant levels of prime editing in the retina, protein expression restoration and partial visual function rescue. Optimized PE-eVLPs support transient in vivo delivery of prime editor ribonucleoproteins, enhancing the potential safety of prime editing by reducing off-target editing and obviating the possibility of oncogenic transgene integration.

DOI: 10.1038/s41587-023-02078-y

Source: https://www.nature.com/articles/s41587-023-02078-y