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Guiding bacteria with small molecules and RNA.

ABSTRACT: Chemotactic bacteria navigate their chemical environment by coupling sophisticated information processing capabilities to molecular motors that propel the cells forward. The ability to reprogram bacteria to follow entirely new chemical signals would create powerful new opportunities in bioremediation, bionanotechnology, and synthetic biology. However, the complexities of bacterial signaling and limitations of current protein engineering methods combine to make reprogramming bacteria to follow novel molecules a difficult task. Here we show that by using a synthetic riboswitch rather than an engineered protein to recognize a ligand, E. coli can be guided toward and precisely localized to a completely new chemical signal.

SUBMITTER: Topp S

PROVIDER: S-EPMC2564849 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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Guiding bacteria with small molecules and RNA.

Topp Shana S Gallivan Justin P JP

Journal of the American Chemical Society 20070505 21

Chemotactic bacteria navigate their chemical environment by coupling sophisticated information processing capabilities to molecular motors that propel the cells forward. The ability to reprogram bacteria to follow entirely new chemical signals would create powerful new opportunities in bioremediation, bionanotechnology, and synthetic biology. However, the complexities of bacterial signaling and limitations of current protein engineering methods combine to make reprogramming bacteria to follow no ...[more]

PMID: 17480075

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Project description:RNA-based therapies, including RNA molecules as drugs and RNA-targeted small molecules, offer unique opportunities to expand the range of therapeutic targets. Various forms of RNAs may be used to selectively act on proteins, transcripts, and genes that cannot be targeted by conventional small molecules or proteins. Although development of RNA drugs faces unparalleled challenges, many strategies have been developed to improve RNA metabolic stability and intracellular delivery. A number of RNA drugs have been approved for medical use, including aptamers (e.g., pegaptanib) that mechanistically act on protein target and small interfering RNAs (e.g., patisiran and givosiran) and antisense oligonucleotides (e.g., inotersen and golodirsen) that directly interfere with RNA targets. Furthermore, guide RNAs are essential components of novel gene editing modalities, and mRNA therapeutics are under development for protein replacement therapy or vaccination, including those against unprecedented severe acute respiratory syndrome coronavirus pandemic. Moreover, functional RNAs or RNA motifs are highly structured to form binding pockets or clefts that are accessible by small molecules. Many natural, semisynthetic, or synthetic antibiotics (e.g., aminoglycosides, tetracyclines, macrolides, oxazolidinones, and phenicols) can directly bind to ribosomal RNAs to achieve the inhibition of bacterial infections. Therefore, there is growing interest in developing RNA-targeted small-molecule drugs amenable to oral administration, and some (e.g., risdiplam and branaplam) have entered clinical trials. Here, we review the pharmacology of novel RNA drugs and RNA-targeted small-molecule medications, with a focus on recent progresses and strategies. Challenges in the development of novel druggable RNA entities and identification of viable RNA targets and selective small-molecule binders are discussed. SIGNIFICANCE STATEMENT: With the understanding of RNA functions and critical roles in diseases, as well as the development of RNA-related technologies, there is growing interest in developing novel RNA-based therapeutics. This comprehensive review presents pharmacology of both RNA drugs and RNA-targeted small-molecule medications, focusing on novel mechanisms of action, the most recent progress, and existing challenges.

Dataset Information

Guiding bacteria with small molecules and RNA.

Publications

Guiding bacteria with small molecules and RNA.

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