Peptide nucleic acid (PNA) binding-mediated gene regulation

Wang, Gan; Xu, Xiaoxin

doi:10.1038/sj.cr.7290209

Cited by 47 publications

(41 citation statements)

References 63 publications

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“…These properties of PNA oligomers make PNAs an ideal candidate for the antisense or antigene applications. Because PNAs are not substrates for the RNase-H or other RNases, the antisense mechanism of PNAs depends on steric hindrance [42].…”

Section: Peptide Nucleic Acids (Pnas)mentioning

confidence: 99%

Antisense Technology: A Selective Tool for Gene Expression Regulation and Gene Targeting

Sahu¹,

Shilakari²,

Nayak³

et al. 2007

CPB

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This review deals with the antisense technology that, together, forms a very powerful tool to inhibit gene expression and may be used for studying gene function (functional genomics) and for therapeutic purpose (antisense gene therapy). Antisense oligonucleotides block translation of target mRNAs in a sequence specific manner, either by steric blocking of translation or by destruction of the bound mRNA via RNase-H enzyme. For proper designing, accessible sites of the target RNA for binding antisense oligonucleotides have to be identified. Whether being used as an experimental reagent or pharmaceuticals, several problems or drawbacks have to be overcome for successful applications. Toward this direction, various modifications of sugar, bases and phosphate backbone of antisense oligonucleotides have been attempted. In recent years valuable progress has been achieved through the development of advanced cellular delivery systems and novel chemically modified nucleotides with improved properties such as enhanced serum stability, higher target affinity and low toxicity. These qualities and the specificity of binding make this technique a potentially powerful therapeutic tool for gene targeting and/ or expression regulation. This review discusses the basis of structural design, mode of action, chemical modification, enhanced cellular uptake, therapeutic application and future possibilities in the field of advanced antisense technology.

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Section: Peptide Nucleic Acids (Pnas)mentioning

confidence: 99%

Antisense Technology: A Selective Tool for Gene Expression Regulation and Gene Targeting

Sahu¹,

Shilakari²,

Nayak³

et al. 2007

CPB

View full text Add to dashboard Cite

show abstract

“…Attaching a positively charged peptide to PNA enhances hybridization [17,18] and, moreover, the use of PNA binding in both Watson-Crick and Hoogsteen modes, i.e., bis-PNA, as well as the presence of hybridized ''openers'' [19,20], further facilitates binding. Unlike modifications in the PNA structure, which can enhance both the specificity and affinity as observed for, e.g., bis-PNA [21] and pseudocomplementary PNA [22], most changes of the environmental parameters will influence either the affinity or the specificity [23].…”

Section: Introductionmentioning

confidence: 97%

Temperature-Assisted Cyclic Hybridization (TACH): An Improved Method for Supercoiled DNA Hybridization

et al. 2010

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Accurate hybridization is dependent on the ratio between sequence-specific and unspecific binding. Dissociation of unspecifically bound, while maintaining specifically hybridized, nucleic acids are key steps to obtain a well-defined complex. We have developed a new method, temperature-assisted, cyclic hybridization (TACH), which increases cognate binding at the expense of unspecific hybridization. The method was used for optimizing binding of peptide nucleic acid (PNA) to supercoiled plasmids and has several advantages over previous methods: (1) it reduces the required amount of bis-PNA by three- to fourfold; (2) it results in less unspecific binding; (3) it extends cooperative hybridization, from 3 bp to 5 bp between two adjacent binding sites; and (4) it decreases the aggregation of bis-PNA. This method might be extended to other forms of hybridizations including the use of additional nucleic acids analogs, such as locked nucleic acid (LNA) and, also, to other areas where PNAs are used such as fluorescence in situ hybridization (FISH), microarrays, or in vivo plasmid delivery.

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“…PNA exhibits a thermodynamically and kinetically improved hybridization behavior as compared to DNA and RNA, mainly due to the non-charged PNA backbone. [8,9] The high selectivity and excellent discrimination of single-nucleotide polymorphism (SNP), [10,11] combined with an improved chemical stability towards nucleases and proteases, [12] is the basis for the increasing attractiveness of PNA for bioanalytical applications, [11] and for antigene/antisense therapy [13,14] or drug discovery. [15] The core of any DNA biosensor is the detection of the hybridization event between immobilized nucleic acid capture probes and a specific target DNA analyte in solution.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic Studies of Fc‐PNA(⋅DNA) Surface Dynamics Based on the Kinetics of Electron‐Transfer Processes

Hüsken

Gębala

Mantia

et al. 2011

Chemistry A European J

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N-Terminally ferrocenylated and C-terminally gold-surface-grafted peptide nucleic acid (PNA) strands were exploited as unique tools for the electrochemical investigation of the strand dynamics of short PNA(⋅DNA) duplexes. On the basis of the quantitative analysis of the kinetics and the diffusional characteristics of the electron-transfer process, a nanoscopic view of the Fc-PNA(⋅DNA) surface dynamics was obtained. Loosely packed, surface-confined Fc-PNA single strands were found to render the charge-transfer process of the tethered Fc moiety diffusion-limited, whereas surfaces modified with Fc-PNA⋅DNA duplexes exhibited a charge-transfer process with characteristics between the two extremes of diffusion and surface limitation. The interplay between the inherent strand elasticity and effects exerted by the electric field are supposed to dictate the probability of a sufficient approach of the Fc head group to the electrode surface, as reflected in the measured values of the electron-transfer rate constant, k(0). An in-depth understanding of the dynamics of surface-bound PNA and PNA⋅DNA strands is of utmost importance for the development of DNA biosensors using (Fc-)PNA recognition layers.

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Peptide nucleic acid (PNA) binding-mediated gene regulation

Cited by 47 publications

References 63 publications

Antisense Technology: A Selective Tool for Gene Expression Regulation and Gene Targeting

Antisense Technology: A Selective Tool for Gene Expression Regulation and Gene Targeting

Temperature-Assisted Cyclic Hybridization (TACH): An Improved Method for Supercoiled DNA Hybridization

Mechanistic Studies of Fc‐PNA(⋅DNA) Surface Dynamics Based on the Kinetics of Electron‐Transfer Processes

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