Small RNA-based systems for sensing and therapeutic applications

Penchovsky, Robert; Miloshev, Georgi Y.; Pavlova, Nikolet; Popova, Katya B.; Valsamatzi-Panagiotou, Aikaterini; Otcheva, Lozena A.; Traykovska, Martina

doi:10.1016/b978-0-12-824469-2.00004-x

Cited by 3 publications

(10 citation statements)

References 71 publications

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“…(B) The spliced mRNAs are transferred from the nucleus (1). Ribosomal subunits recognize RBS and bind (2). The ribozyme binding triggers translation (3) and protein expression (4).…”

Section: Aso-based Strategies For Drug Developmentmentioning

confidence: 99%

“…For instance, short hairpin RNA (shRNA) and bifunctional short hairpin RNA (bi-shRNA) can inhibit target wild mRNAs or mutate mRNAs [46]. (2). Through the action of the Dicer enzyme, which is part of the RNA interference complex, the non-coding hairpin RNA-2 and hairpin RNA-1 are formed (3).…”

Section: Rnaimentioning

confidence: 99%

“…At the same time, new natural mechanisms for the control of gene expression have been discovered based on various types of RNAs, including micro(mi)RNAs, small interfering(si)RNAs, riboswitches [ 1 ], and ribozymes. There are currently four different nucleic acid engineering strategies to inhibit the expression of specific RNAs in the cell, such as siRNAs [ 2 ], antisense oligonucleotides (ASOs) [ 3 ], ribozymes [ 4 , 5 ], and CRISPR-Cas9 systems [ 6 ]. All tools used for nucleic acid-based drug development are inherited based on rational design methods, being novel and the main point of this review.…”

Section: Introductionmentioning

confidence: 99%

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Antisense and Functional Nucleic Acids in Rational Drug Development

Penchovsky,

Georgieva,

Dyakova

et al. 2024

Antibiotics

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This review is focused on antisense and functional nucleic acid used for completely rational drug design and drug target assessment, aiming to reduce the time and money spent and increase the successful rate of drug development. Nucleic acids have unique properties that play two essential roles in drug development as drug targets and as drugs. Drug targets can be messenger, ribosomal, non-coding RNAs, ribozymes, riboswitches, and other RNAs. Furthermore, various antisense and functional nucleic acids can be valuable tools in drug discovery. Many mechanisms for RNA-based control of gene expression in both pro-and-eukaryotes and engineering approaches open new avenues for drug discovery with a critical role. This review discusses the design principles, applications, and prospects of antisense and functional nucleic acids in drug delivery and design. Such nucleic acids include antisense oligonucleotides, synthetic ribozymes, and siRNAs, which can be employed for rational antibacterial drug development that can be very efficient. An important feature of antisense and functional nucleic acids is the possibility of using rational design methods for drug development. This review aims to popularize these novel approaches to benefit the drug industry and patients.

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“…(B) The spliced mRNAs are transferred from the nucleus (1). Ribosomal subunits recognize RBS and bind (2). The ribozyme binding triggers translation (3) and protein expression (4).…”

Section: Aso-based Strategies For Drug Developmentmentioning

confidence: 99%

Section: Rnaimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Antisense and Functional Nucleic Acids in Rational Drug Development

Penchovsky,

Georgieva,

Dyakova

et al. 2024

Antibiotics

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“…Methods of synthetic biology can be employed not only to develop but also to produce new antibiotics. 20,21 ■ MATERIALS AND METHODS Bioinformatics Databases. The aptamer sequences of the TPP riboswitch in several bacteria were obtained from the RSwitch https:// penchovsky.atwebpages.com/applications.php?page=58 databases.…”

Section: ■ Introductionmentioning

confidence: 99%

“…When these two pathways are inhibited, the bacteria cannot survive. Methods of synthetic biology can be employed not only to develop but also to produce new antibiotics. , …”

Section: Introductionmentioning

confidence: 99%

Targeting TPP Riboswitches Using Chimeric Antisense Oligonucleotide Technology for Antibacterial Drug Development

Traykovska

Otcheva

Penchovsky

2022

ACS Appl. Bio Mater.

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Nowadays, the emergence and the transmission of multidrug-resistant pathogenic bacteria are a severe menace mounting a lot of pressure on the healthcare systems worldwide. Many severe outbreaks of bacterial infections have been reported worldwide in recent years. Thus, there is an immediate demand to develop antibiotics. Some riboswitches are potential targets for overcoming bacterial resistance. This paper demonstrates the bacteriostatic effect of an antisense oligonucleotide (ASO) engineered to suppress the growth of pathogenic bacteria such as Listeria monocytogenes by targeting the Thiamine Pyrophosphate (TPP) riboswitch. It does not inhibit the growth of the conditional pathogenic bacteria Escherichia coli, as it lacks the TPP riboswitch, showing the specificity of action of our ASO. It is covalently bonded with the cell-penetrating protein pVEC. We did bioinformatics analyses of the thiamine pyrophosphate riboswitch regarding its role in synthesizing the metabolite thiamine pyrophosphate, which is essential for bacteria. L. monocytogenes is intrinsically resistant to cephalosporins and usually is treated with ampicillin. A dosage of ASO has been established that inhibits 80% of bacterial growth at 700 nM (4.5 μg/mL). Thus, the TPP riboswitch is a valuable antibacterial target.

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Highly nonlinear optic nucleic acid thin-solid film to generate short pulse laser

Ghasemi,

Debnath,

Kim

et al. 2023

Sci Rep

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Using aqueous precursors, we report successfully fabricating thin-solid films of two nucleic acids, ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). We investigated the potential of these films deposited on a fiber optic platform as all-fiber integrated saturable absorbers (SAs) for ultrafast nonlinear optics. RNA-SA performances were comparable to those of DNA-SA in terms of its nonlinear transmission, modulation depth, and saturation intensity. Upon insertion of these devices into an Erbium-doped fiber ring-laser cavity, both RNA and DNA SAs enabled efficient passive Q-switching operation. RNA-SA application further facilitated robust mode-locking and generated a transform-limited soliton pulse, exhibiting a pulse duration of 633 femtoseconds. A detailed analysis of these pulsed laser characteristics compared RNA and DNA fiber optic SAs with other nonlinear optic materials. The findings of this research establish the feasibility of utilizing RNA as a saturable absorber in ultrafast laser systems with an equal or higher potential as DNA, which presents novel possibilities for the nonlinear photonic applications of nucleic acid thin solid films.

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Small RNA-based systems for sensing and therapeutic applications

Cited by 3 publications

References 71 publications

Antisense and Functional Nucleic Acids in Rational Drug Development

Antisense and Functional Nucleic Acids in Rational Drug Development

Targeting TPP Riboswitches Using Chimeric Antisense Oligonucleotide Technology for Antibacterial Drug Development

Highly nonlinear optic nucleic acid thin-solid film to generate short pulse laser

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