Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Mol Cell. 2017 Jun 1;66(5):721-728.e3. doi: 10.1016/j.molcel.2017.04.025. Epub 2017 May 25.
A major limitation in using bacteriophage-based applications is their narrow host range. Approaches for extending the host range have focused primarily on lytic phages in hosts supporting their propagation rather than approaches for extending the ability of DNA transduction into phage-restrictive hosts. To extend the host range of T7 phage for DNA transduction, we have designed hybrid particles displaying various phage tail/tail fiber proteins. These modular particles were programmed to package and transduce DNA into hosts that restrict T7 phage propagation. We have also developed an innovative generalizable platform that considerably enhances DNA transfer into new hosts by artificially selecting tails that efficiently transduce DNA. In addition, we have demonstrated that the hybrid particles transduce desired DNA into desired hosts. This study thus critically extends and improves the ability of the particles to transduce DNA into novel phage-restrictive hosts, providing a platform for myriad applications that require this ability.
基于噬菌体的应用的一个主要限制因素是其宿主范围狭窄。扩展宿主范围的方法主要集中在支持其繁殖的裂解噬菌体上,而不是扩展将 DNA 转导到噬菌体限制宿主的能力的方法。为了扩展 T7 噬菌体用于 DNA 转导的宿主范围,我们设计了显示各种噬菌体尾部/尾部纤维蛋白的混合颗粒。这些模块化颗粒被编程为包装和转导 DNA 进入限制 T7 噬菌体繁殖的宿主。我们还开发了一种创新的可推广平台,通过人工选择能够有效转导 DNA 的尾部,极大地提高了 DNA 向新宿主的转移效率。此外,我们已经证明了混合颗粒可以将所需的 DNA 转导到所需的宿主中。因此,这项研究极大地扩展和提高了颗粒将 DNA 转导到新型噬菌体限制宿主的能力,为需要这种能力的众多应用提供了一个平台。