true-amino-peptides Triplex-forming peptide nucleic acids (PNAs) represent a significant advancement in molecular biology and genetic engineering, offering a versatile platform for sequence-specific recognition and manipulation of nucleic acids作者:T Sato·2016·被引用次数:102—The present work demonstrates that sequence-selective recognition of duplex RNA can be achieved under physiol.. These synthetic analogues of DNA and RNA possess a unique chemical structure that enables them to form stable triplexes with double-stranded DNA and RNA作者:D Hnedzko·2019·被引用次数:6—Thetriplex-forming PNAsrepresent a new approach for RNA recognition that may find future applications in fundamental science, biotechnology and medicine.. This capability has opened new avenues for research in fields ranging from fundamental gene expression studies to the development of novel therapeutic strategies.
Understanding the Structure and Formation of Triplexes
At the core of triplex-forming peptide nucleic acids (PNAs) is their ability to bind to a DNA or RNA double helix in a third strand, forming a stable triple helixPeptide Nucleic Acids (PNAs), introduced by Nielsen et al. in 1991,are synthetic DNA/RNA analoguesand represent a promising tool for gene modulation in .... Unlike natural nucleic acids, PNAs feature a backbone composed of repeating N-(2-aminoethyl)glycine units, linked by peptide bonds, instead of a sugar-phosphate structure. This modification confers several advantageous properties, including enhanced binding affinity, resistance to nucleases, and improved cellular uptakeTriplex-Forming Peptide Nucleic Acid Probes Having ....
The formation of a triplex involves the binding of the PNA strand to the major groove of a pre-existing DNA or RNA double helix.作者:V Kumar·2020·被引用次数:14—Peptide nucleic acid (PNA) forms a triple helixwith double-stranded RNA (dsRNA) stabilized by a hydrogen-bonding zipper formed by PNA's ... This binding is highly sequence-specific, relying on Watson-Crick base pairing principles. For instance, a polypurine peptide nucleic acid can bind to a polypyrimidine-purine sequence within a DNA double helix. This interaction is often stabilized by a "hydrogen-bonding zipper" formed by the backbone amides of the PNA, as demonstrated in studies involving peptide nucleic acid (PNA) forms a triple helix with double-stranded RNA (dsRNA). The high affinity of triplex-forming peptide nucleic acids (PNAs) for specific DNA or RNA sequences, including their ability to bind to single-purine-nucleotide bulges in double-stranded DNA, further underscores their precision. Researchers have also explored modifications to the nucleobases of triplex-forming peptide nucleic acid (PNA) probes, such as incorporating thiazole orange, to enhance their detection capabilities for targets like double-stranded RNA.
Applications in Genetics and Therapeutics
The unique properties of triplex-forming peptide nucleic acids (PNAs) have led to their exploration in a variety of groundbreaking applications. One significant area is triplex-forming PNA-induced donor DNA recombination. This mechanism allows for precise gene editing by guiding a donor DNA template to a specific chromosomal target. This has been successfully harnessed to create mutations that increase the expression of genes like $\gamma$-globin in adult mammalian cells, offering potential therapeutic strategies for conditions like hereditary persistence of fetal hemoglobin (HPFH).
Furthermore, triplex-forming PNAs are emerging as powerful tools for RNA recognition.A new Peptide Nucleic Acid (PNA) structure with potential ... They can bind sequence-specifically to double-stranded RNA (dsRNA), a crucial step in various biological processes and a target for therapeutic intervention. This ability for sequence-specific recognition of double-stranded RNA using peptide nucleic acids (PNAs) that form triple helices is opening doors for modulating gene expression at the post-transcriptional level.
Beyond gene editing and RNA targeting, triplex-forming peptide nucleic acids are being investigated for diagnostic and therapeutic purposes. For example, triplex-forming peptide nucleic acid (PNA) probes labeled with fluorescent markers can be used for the fluorogenic sensing of specific nucleic acid structures.作者:N Brodyagin·2021·被引用次数:78—PNA was originally designed as a DNA mimicto improve the properties of triplex-forming oligonucleotides [1,2]. Two key considerations were elimination of ... The incorporation of modified nucleobases, such as thio-pseudoisocytosine into triplex-forming PNAs, can further enhance their utility for targeting duplex regions in RNAs for biological and therapeutic applications.作者:N Brodyagin·2020·被引用次数:15—We describe a method for sequence-specific recognition of double-stranded RNA usingpeptide nucleic acids (PNAs) that form triple helicesin the major grove of ... The development of nanoparticles that deliver triplex-forming peptide nucleic acids in conjunction with donor DNA is a promising approach for in vivo gene correction, as evidenced by efforts to correct the F508del mutationTriplex-forming peptide nucleic acids (PNAs)have gained recognition as effective ligands for binding double-stranded RNA, offering high sequence ....
Bridging the Gap: PNA as a DNA Mimic
The development of triplex-forming PNAs can be traced back to the initial design of peptide nucleic acid (PNA) as a DNA mimic.Triplex-Forming Peptide Nucleic Acid Controls Dynamic ... The goal was to improve upon the properties of natural oligonucleotides used for triplex formation, such as triplex-forming oligonucleotides (TFOs).作者:M Katkevics·2024·被引用次数:21—In the expanding area of RNA research,peptide nucleic acid (PNA) is emerging as a promising ligand for triple-helical recognition of complex RNAs. Key considerations included the elimination of the natural sugar-phosphate backbone, which is susceptible to degradation, and the enhancement of binding affinity.Triplex-Forming Peptide Nucleic Acids with Extended ... Indeed, PNA was originally designed as a DNA mimic to improve the properties of triplex-forming oligonucleotides. This foundational work has paved the way for the sophisticated applications we see today. Researchers have even explored novel peptide nucleic acid (PNA) structures, such as those with extended backbones, to refine the triple helix formation and improve targeting capabilities.
Future Directions and Potential Impact
The field of triplex-forming peptide nucleic acids is continuously evolving.Peptide Nucleic Acids (PNAs), introduced by Nielsen et al. in 1991,are synthetic DNA/RNA analoguesand represent a promising tool for gene modulation in ... Ongoing research focuses on optimizing PNA design, improving delivery methods, and expanding their therapeutic applications. The ability of triplex formation to interfere with protein binding to DNA and alter gene expression during transcription is a compelling area of investigation for developing novel gene silencing or activation strategies. As our understanding of triplex-forming peptide nucleic acids (PNAs) deepens, they are poised to become indispensable tools in the arsenal of geneticists, molecular biologists, and clinicians, offering unprecedented control over genetic material for both research and the treatment of disease.作者:V Kumar·2020·被引用次数:14—Peptide nucleic acid (PNA) forms a triple helixwith double-stranded RNA (dsRNA) stabilized by a hydrogen-bonding zipper formed by PNA's ... The inherent stability and sequence-specificity of these molecules make them a promising avenue for future biotechnological and medical advancements. The broad utility of forming peptide nucleic acids as ligands for binding double-stranded RNA further highlights their significance.
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