Antisense and Antigene Properties of Peptide Nucleic Acids

Hanvey, Jeffery C.; Peffer, Nancy J.; Bisi, John E.; Thomson, Stephen A.; Cadilla, Rodolfo; Josey, John A.; Ricca, Daniel J.; Hassman, C. Fred; Bonham, Michele A.; Au, Karin G.; Carter, Stephen G.; Bruckenstein, David A.; Boyd, Ann L.; Noble, Stewart A.; Babiss, Lee E.

doi:10.1126/science.1279811

Cited by 534 publications

(299 citation statements)

References 15 publications

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“…Based on this property, PNAs have great potential as DNA targeting "drugs" [64]. Moreover, PNAs are resistant to both nucleases and proteases, and their neutral backbone increases their hybridization affinities to complementary RNA and DNA strands [65]. PNAs have been used successfully to target chromosomal DNA at transcription start sites to inhibit gene expression in cells [66][67][68].…”

Section: Chemical Modifications Of Tfosmentioning

confidence: 99%

DNA triple helices: Biological consequences and therapeutic potential

Jain

Wang²,

Vásquez³

2008

Biochimie

269

199

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DNA structure is a critical element in determining its function. The DNA molecule is capable of adopting a variety of non-canonical structures, including three-stranded (i.e. triplex) structures, which will be the focus of this review. The ability to selectively modulate the activity of genes is a longstanding goal in molecular medicine. DNA triplex structures, either intermolecular triplexes formed by binding of an exogenously applied oligonucleotide to a target duplex sequence, or naturally occurring intramolecular triplexes (H-DNA) formed at endogenous mirror repeat sequences, present exploitable features that permit site-specific alteration of the genome. These structures can induce transcriptional repression and site-specific mutagenesis or recombination. Triplex-forming oligonucleotides (TFOs) can bind to duplex DNA in a sequence specific fashion with high affinity, and can be used to direct DNA-modifying agents to selected sequences. H-DNA plays important roles in vivo and is inherently mutagenic and recombinogenic, such that elements of the H-DNA structure may be pharmacologically exploitable. In this review we discuss the biological consequences and therapeutic potential of triple helical DNA structures. We anticipate that the information provided will stimulate further investigations aimed toward improving DNA triplexrelated gene targeting strategies for biotechnological and potential clinical applications.

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Section: Chemical Modifications Of Tfosmentioning

confidence: 99%

DNA triple helices: Biological consequences and therapeutic potential

Jain

Wang²,

Vásquez³

2008

Biochimie

269

199

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“…1,4 Despite their enormous potential as therapeutic agents, reports of poor cellular uptake, due to their low phospholipid permeability, dampened the initial enthusiasm. [5][6][7][8] However, early studies on PNA import were limited to a small number of different cell lines and import conditions. In addition, it is well recognised that oligodeoxynucleotide uptake can differ markedly between different cell types.…”

Section: Introductionmentioning

confidence: 99%

Peptide nucleic acid delivery to human mitochondria

et al. 1999

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Peptide nucleic acids (PNAs) are synthetic polynucleobase as therapeutic agents for mtDNA disease, we attempted to molecules, which bind to DNA and RNA with high affinity localise PNAs to the mitochondrial matrix. When attached and specificity. Although PNAs have enormous potential to the presequence peptide of the nuclear-encoded human as anti-sense agents, the success of PNA-mediated gene cytochrome c oxidase (COX) subunit VIII, the biotinylated therapy will require efficient cellular uptake and sub-cellular PNA was successfully imported into isolated organelles in trafficking. At present these mechanisms are poorly undervitro. Furthermore, delivery of the biotinylated peptide-PNA stood. To address this, we have studied the uptake of biotito mitochondria in intact cells was confirmed by confocal nylated PNAs into cultured cell lines using fluorescence microscopy. These studies demonstrate that biotinylated confocal microscopy. In human myoblasts, initial punctate PNAs can be directed across cell membranes and to a staining was followed by the release of PNAs into the cytospecific sub-cellular compartment within human cellssol and subsequent localisation and concentration in the highlighting the importance of these novel molecules for nucleus. To determine whether PNAs could also be used human gene therapy.

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“…These include locked nucleic acids (LNA) in which an extra link between the 2 0 -O and the 4 0 -C ''locks'' the ribose group, phosphorothioate substituted nucleic acids (PS), peptide nucleic acids (PNAs), in which the bases are linked to the backbone by methylene carbonyl bonds (Hanvey et al, 1992;Obika et al, 2001;Wahlestedt et al, 2000;Woolf et al, 1990) and fully modified 2 0 -O-methyl oligonucleotides (Schneider et al, 2011). Each of these methods has been validated in Xenopus.…”

Section: Controlling Translation With Small Moleculesmentioning

confidence: 99%

Xenopus: An ideal system for chemical genetics

Wheeler

Liu

2012

Genesis

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Summary: Chemical genetics, or chemical biology, has become an increasingly powerful method for studying biological processes. The main objective of chemical genetics is the identification and use of small molecules that act directly on proteins, allowing rapid and reversible control of activity. These compounds are extremely powerful tools for researchers, particularly in biological systems that are not amenable to genetic methods. In addition, identification of small molecule interactions is an important step in the drug discovery process. Increasingly, the African frog Xenopus is being used for chemical genetic approaches. Here, we highlight the advantages of Xenopus as a first-line in vivo model for chemical screening as well as for testing reverse engineering approaches. genesis 50: 207-218, 2012. V V C 2012 Wiley Periodicals, Inc.

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Antisense and Antigene Properties of Peptide Nucleic Acids

Cited by 534 publications

References 15 publications

DNA triple helices: Biological consequences and therapeutic potential

DNA triple helices: Biological consequences and therapeutic potential

Peptide nucleic acid delivery to human mitochondria

Xenopus: An ideal system for chemical genetics

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