Bacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
Bacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
Curr Opin Virol. 2022 Aug;55:101255. doi: 10.1016/j.coviro.2022.101255. Epub 2022 Aug 8.
The ability to deliver therapeutic genes and biomolecules into a human cell and restore a defective function has been the holy grail of medicine. Adeno-associated viruses and lentiviruses have been extensively used as delivery vehicles, but their capacity is limited to one (or two) gene(s). Bacteriophages are emerging as novel vehicles for gene therapy. The large 120 × 86-nm T4 capsid allows engineering of both its surface and its interior to incorporate combinations of DNAs, RNAs, proteins, and their complexes. In vitro assembly using purified components allows customization for various applications and for individualized therapies. Its large capacity, cell-targeting capability, safety, and inexpensive manufacturing could open unprecedented new possibilities for gene, cancer, and stem cell therapies. However, efficient entry into primary human cells and intracellular trafficking are significant barriers that must be overcome by gene engineering and evolution in order to translate phage-delivery technology from bench to bedside.
将治疗性基因和生物分子递送到人体细胞中并恢复其缺陷功能一直是医学的圣杯。腺相关病毒和慢病毒已被广泛用作递送载体，但它们的容量仅限于一个（或两个）基因。噬菌体作为基因治疗的新型载体正在兴起。大型 120×86nm T4 衣壳允许对其表面和内部进行工程改造，以纳入 DNA、RNA、蛋白质及其复合物的组合。使用纯化组件进行体外组装可针对各种应用和个体化治疗进行定制。其大容量、细胞靶向能力、安全性和廉价的制造可能为基因、癌症和干细胞治疗开辟前所未有的新可能性。然而，高效进入原代人细胞和细胞内运输是重大障碍，必须通过基因工程和进化来克服，以便将噬菌体递送技术从实验室转化为临床。
