LNA-modified oligonucleotides effectively drive intramolecular-stable hairpin to intermolecular-duplex state

Kaur, Harleen ; Wengel, Jesper ; Maiti, Souvik (2007) LNA-modified oligonucleotides effectively drive intramolecular-stable hairpin to intermolecular-duplex state Biochemical and Biophysical Research Communications, 352 (1). pp. 118-122. ISSN 0006-291X

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Official URL: http://www.sciencedirect.com/science/article/pii/S...

Related URL: http://dx.doi.org/10.1016/j.bbrc.2006.10.155


Sequence-specific hybridization of antisense and antigene agent to the target nucleic acid is an important therapeutic strategy to modulate gene expression. However, efficiency of such agents falls due to inherent intramolecular-secondary-structures present in the target that pose competition to intermolecular hybridization by complementary antisense/antigene agent. Performance of these agents can be improved by employing structurally modified complementary oligonucleotides that efficiently hybridize to the target and force it to transit from an intramolecular-structured-state to an intermolecular-duplex state. In this study, the potential of variably substituted locked nucleic acid-modified oligonucleotides (8mer) to hybridize and disrupt highly stable, secondary structure of nucleic acid has been biophysically characterized and compared with the conventionally used unmodified DNA oligonucleotides. The target here is a stem–loop hairpin oligonucleotide—a structure commonly present in most structured-nucleic acids and known to exhibit an array of biological functions. Using fluorescence-based studies and EMSA we prove that LNA-modified oligonucleotides hybridize to the target hairpin with higher binding affinity even at lower concentration and subsequently, force it to assume a duplex conformation. LNA-modified oligonucleotides may thus, prove as potential therapeutic candidates to manipulate gene expression by disruption of biologically relevant nucleic acid secondary structure.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Locked Nucleic Acid; Hairpin Trapping; Therapeutic Oligonucleotide
ID Code:103730
Deposited On:31 Mar 2017 07:16
Last Modified:31 Mar 2017 07:16

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