Chemical Tools for Targeted Mutagenesis of DNA Based on Triple Helix Formation

Nagatsugi, Fumi; Sasaki, Shigeki

doi:10.1248/bpb.27.463

Cited by 10 publications

(5 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reference DNA oligonucleotide MPG non-endocytotic [19] antisense PNA penetratin, transportan n. d. [112] antisense PNA transportan n. d. [203] antisense PNA Tat [48][49][50][51][52][53][54][55][56][57][58][59][60] , penetratin, transportan analogues non-endocytotic [205] antisense PNA Tat [48][49][50][51][52][53][54][55][56][57][58] , penetratin, transportan analogues, R 9 F 2 , R 6 -penetratin and further peptides endocytotic (transportan: possibly non-endocytotic) [207] antisense PMO R 9 F 2 (non-covalent + covalent), Tat peptide, penetratin (covalent) n. d. [211] antisense PMO (R-Ahx-R) 4 endocytotic [219] antisense PNA R 6 -penetratin endocytotic [109] antisense PMO (R-Ahx-R) 4 Triple helix-forming oligonucleotides (TFOs) bind as a third strand in the major groove of duplex DNA to form triplex DNA in a sequence-specific manner (for a review see: [226]). Attractive applications of this TFO approach include not only inhibition of the target gene, but also induction of point mutations at predetermined sites.…”

Section: Cargo Cpp/delivery System Proposed Uptake Mechanismmentioning

confidence: 99%

Recent Developments in Peptide-Based Nucleic Acid Delivery

Veldhoen

Laufer

Restle

2008

IJMS

View full text Add to dashboard Cite

Despite the fact that non-viral nucleic acid delivery systems are generally considered to be less efficient than viral vectors, they have gained much interest in recent years due to their superior safety profile compared to their viral counterpart. Among these synthetic vectors are cationic polymers, branched dendrimers, cationic liposomes and cellpenetrating peptides (CPPs). The latter represent an assortment of fairly unrelated sequences essentially characterised by a high content of basic amino acids and a length of 10-30 residues. CPPs are capable of mediating the cellular uptake of hydrophilic macromolecules like peptides and nucleic acids (e.g. siRNAs, aptamers and antisenseoligonucleotides), which are internalised by cells at a very low rate when applied alone. Up to now, numerous sequences have been reported to show cell-penetrating properties and many of them have been used to successfully transport a variety of different cargos into mammalian cells. In recent years, it has become apparent that endocytosis is a major route of internalisation even though the mechanisms underlying the cellular translocation of CPPs are poorly understood and still subject to controversial discussions. In this review, we will summarise the latest developments in peptide-based cellular delivery of nucleic acid cargos. We will discuss different mechanisms of entry, the intracellular fate of the cargo, correlation studies of uptake versus biological activity of the cargo as well as technical problems and pitfalls.

show abstract

Section: Cargo Cpp/delivery System Proposed Uptake Mechanismmentioning

confidence: 99%

Recent Developments in Peptide-Based Nucleic Acid Delivery

Veldhoen

Laufer

Restle

2008

IJMS

View full text Add to dashboard Cite

show abstract

“…(1)) are potentially a prime target for TFOs, a possibility currently under study in collaboration with C. Hélène's former laboratory. Most importantly, as already discussed, albeit tentatively, during the Jacques Monod conferences of 1991 and 1994, the conjugation of such sequence-specific molecules with DNA-damaging/DNA-cleaving agents [79] or topoisomerase poisons opens the way for anti-gene therapeutic approaches and much progress has been made in this area in recent years [83,84]. A related example is that of the attachment of an Fe(II)EDTA cleaving moiety to oligopyrrole dimers, yielding molecules that are active and highly specific for DNA affinity cleavage [51].…”

Section: What Can We Learn From Fliesmentioning

confidence: 92%

Target Practice: Aiming at Satellite Repeats with DNA Minor Groove Binders

Susbielle¹,

Blattes²,

Brevet³

et al. 2005

CMCACA

View full text Add to dashboard Cite

Much progress has been made in recent years in developing small molecules that target the minor groove of DNA. Striking advances have led to the design of synthetic molecules that recognize specific DNA sequences with affinities comparable to those of eukaryotic transcription factors. This makes it feasible to modulate or inhibit DNA/protein interactions in vivo, a major step towards the development of general strategies of anti-gene therapy. Examples from anti-parasitic drugs also suggest that synthetic molecules can affect a variety of cellular functions crucial to cell viability by more generally targeting vast portions of genomes based on their biased base composition. This provides a rationale for developing approaches based on selective interactions with broad genomic targets such as satellite repeats that are associated with structural or architectural components of chromatin essential for cellular proliferation. Using examples drawn from the Drosophila melanogaster model system, we review here the use of synthetic polyamides or diamidines that bind the DNA minor groove and can be used as highly selective agents capable of interfering with specific protein/DNA interactions that occur in A+T-rich repeated sequences that constitute a significant portion of eukaryotic genomes. The satellite localization of cellular proteins that bind the minor groove of DNA via domains such as the AT hook motif is highly sensitive to these molecules. A major consequence of the competition between these proteins and their synthetic mimics is an alteration of the nuclear localization and function of proteins such as topoisomerase II, a major target of anti-cancer drugs.

show abstract

“…Major applications using single-stranded oligonucleotides include an mRNAtargeted antisense method, 1,2 an antigene method based on triplex formation 35 and more recently, a method involving small interfering RNAs (siRNAs): a new class of RNAbased oligonucleotides. 68 The antisense strategy aims to inhibit gene expression through the formation of a DNA RNA hetero duplex between an mRNA target and a singlestranded oligonucleotide with a complementary sequence by WatsonCrick binding (Figure 1). …”

Section: Introductionmentioning

confidence: 99%

“…68,69 Psoralen-linked TFOs were used for photoinduced site-directed mutagenesis in reporter genes ( Figure 24). …”

mentioning

confidence: 99%

Synthesis of Reactive Oligonucleotides for Gene Targeting and Their Application to Gene Expression Regulation

Nagatsugi

Sasaki

2010

Bulletin of the Chemical Society of Japan

Self Cite

View full text Add to dashboard Cite

Many genetic disorders have recently been identified as a major cause of diseases and the regulation of gene expression has been proposed as an attractive therapeutic strategy. Synthetic oligodeoxynucleotides (ODNs) are valuable tools that interfere with gene expression by specifically binding to target genes in a sequence-specific manner. In particular, reactive ODNs are expected to be more efficient because they covalently bind to the target genes. This review summarizes the synthesis of reactive ODNs with inducible reactivity, in particular, their applications to efficient crosslinking reactions, have been developed by the author's group. We also describe applications of the cross-linking reactions to the antisense method in cells and their impact on mutagenesis in model systems.

show abstract

Chemical Tools for Targeted Mutagenesis of DNA Based on Triple Helix Formation

Cited by 10 publications

References 60 publications

Recent Developments in Peptide-Based Nucleic Acid Delivery

Recent Developments in Peptide-Based Nucleic Acid Delivery

Target Practice: Aiming at Satellite Repeats with DNA Minor Groove Binders

Synthesis of Reactive Oligonucleotides for Gene Targeting and Their Application to Gene Expression Regulation

Contact Info

Product

Resources

About