Secreted Particle Information Transfer (SPIT) - A Cellular Platform for In Vivo Genetic Engineering.
Secreted Particle Information Transfer (SPIT) - A Cellular Platform for In Vivo Genetic Engineering.
复制标题
分泌粒子信息传输 (SPIT) - 体内基因工程的细胞平台。
DOI：
10.1101/2024.01.11.575257
复制
发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Nakauchi,Hiromitsu
中科院分区：
文献类型：
--
作者：
Charlesworth,CarstenT;Homma,Shota;Suchy,Fabian;Wang,Sicong;Bhadhury,Joydeep;Amaya,AnaisK;Camarena,Joab;Zhang,Jinyu;Tan,TzeKai;Igarishi,Kyomi;Nakauchi,Hiromitsu
现在有许多工具可以让我们以无数不同的方式精确地操纵人类基因组。然而，将这些工具成功递送到人类患者的细胞仍然是其临床实施的主要障碍。在这里，我们介绍了一种新的细胞体内基因工程的方法，分泌颗粒信息传递（SPIT），利用人类细胞作为体内基因工程的传递载体。我们展示了SPIT用于Cre重组酶和CRISPR-Cas9酶的细胞-细胞递送的应用，我们表明遗传逻辑可以并入SPIT中，并首次展示了人类细胞作为免疫活性小鼠体内遗传工程的递送平台。我们成功地将SPIT应用于体内多个器官和组织干细胞的遗传修饰，包括肝、脾、肠、外周血和骨髓。我们预计，通过利用人类细胞核的大包装能力、人类细胞长期植入患者体内的能力以及人类细胞进行复杂遗传编程的能力，SPIT将成为体内遗传工程的范式转变方法。
A multitude of tools now exist that allow us to precisely manipulate the human genome in a myriad of different ways. However, successful delivery of these tools to the cells of human patients remains a major barrier to their clinical implementation. Here we introduce a new cellular approach for in vivo genetic engineering, Secreted Particle Information Transfer (SPIT) that utilizes human cells as delivery vectors for in vivo genetic engineering. We demonstrate the application of SPIT for cell-cell delivery of Cre recombinase and CRISPR-Cas9 enzymes, we show that genetic logic can be incorporated into SPIT and present the first demonstration of human cells as a delivery platform for in vivo genetic engineering in immunocompetent mice. We successfully applied SPIT to genetically modify multiple organs and tissue stem cells in vivo including the liver, spleen, intestines, peripheral blood, and bone marrow. We anticipate that by harnessing the large packaging capacity of a human cell’s nucleus, the ability of human cells to engraft into patients’ long term and the capacity of human cells for complex genetic programming, that SPIT will become a paradigm shifting approach for in vivo genetic engineering.