An RNA biology perspective on species‐specific programmable RNA antibiotics,Molecular Microbiology

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An RNA biology perspective on species‐specific programmable RNA antibiotics
Molecular Microbiology ( IF 2.6 ) Pub Date : 2020-03-17 , DOI: 10.1111/mmi.14476
Jörg Vogel _{1,

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Affiliation

Our body is colonized by a vast array of bacteria the sum of which forms our microbiota. The gut alone harbors >1,000 bacterial species. An understanding of their individual or synergistic contributions to human health and disease demands means to interfere with their functions on the species level. Most of the currently available antibiotics are broad‐spectrum, thus too unspecific for a selective depletion of a single species of interest from the microbiota. Programmable RNA antibiotics in the form of short antisense oligonucleotides (ASOs) promise to achieve precision manipulation of bacterial communities. These ASOs are coupled to small peptides that carry them inside the bacteria to silence mRNAs of essential genes, for example, to target antibiotic‐resistant pathogens as an alternative to standard antibiotics. There is already proof‐of‐principle with diverse bacteria, but many open questions remain with respect to true species specificity, potential off‐targeting, choice of peptides for delivery, bacterial resistance mechanisms and the host response. While there is unlikely a one‐fits‐all solution for all microbiome species, I will discuss how recent progress in bacterial RNA biology may help to accelerate the development of programmable RNA antibiotics for microbiome editing and other applications.

中文翻译：

RNA生物学对物种特异性可编程RNA抗生素的看法

我们的身体被各种各样的细菌殖民，这些细菌的总和构成了我们的微生物群。仅肠道就含有超过1,000种细菌。了解它们对人类健康和疾病需求的个体或协同作用意味着在物种层面上干扰其功能。目前大多数可用的抗生素都是广谱的，因此对于从微生物群中选择性地去除感兴趣的单一物种而言，其特异性太强。短反义寡核苷酸（ASO）形式的可编程RNA抗生素有望实现对细菌群落的精确控制。这些ASO与小肽偶联，这些小肽携带它们进入细菌内部，以沉默必需基因的mRNA，例如，靶向抗药性病原体作为标准抗生素的替代品。已经有多种细菌的原理证明，但是关于真正的物种特异性，潜在的脱靶，用于输送的肽选择，细菌抗性机制和宿主反应，仍然存在许多悬而未决的问题。尽管不可能为所有微生物组提供一种万能的解决方案，但我将讨论细菌RNA生物学的最新进展如何有助于加快用于微生物组编辑和其他应用的可编程RNA抗生素的开发。

更新日期：2020-03-26

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