Designing Antisense Oligonucleotides
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Restoration of correct splicing in IVSI-110 mutation of β-globin gene with antisense oligonucleotides: implications and applications in functional assay development
Objective(s): The use of antisense oligonucleotides (AOs) to restore normal splicing by blocking the recognition of aberrant splice sites by the spliceosome represents an innovative means of potentially controlling certain inherited disorders affected by aberrant splicing. Selection of the appropriate target site is essential in the success of an AO therapy. In this study, in search for a splic...
متن کاملDesigning Antisense Oligonucleotides
Antisense oligonucleotides have been used for a number of years to modify the expression of specific genes both in vivo and in vitro (Scanlon et al., 1995). The most potent mode of antisense activity is through RNase H–mediated degradation of RNA (Figure 1). The RNase H– endonuclease specifically cleaves RNA only when it is hybridized as a heteroduplex with DNA. In general, oligonucleotides tha...
متن کاملSpecific Inhibition of the Expression of the Promyelocytic Leukemia (PML) Protein by Anti-Sense Oligonucleotides
In the present study, using anti-sense oligonucleotides the inhibition of expression of the PML protein hasbeen investigated. The anti-sense oligonucleotides were designed against the translation initiation site ofthe PML gene, and their effects were investigated on cellular growth and DNA synthesis. Incubation of normalhuman fibroblast cells with the anti-sense oligonucleotid...
متن کاملExpanding the design horizon of antisense oligonucleotides with alpha-L-LNA.
Oligonucleotides containing Locked Nucleic Acids (LNA) to various extents and at various positions were evaluated for antisense activity, RNase H recruitment, nuclease stability and thermal affinity. In this work, two different diastereoisomers of LNA were studied: the beta-D-LNA and the alpha-L-LNA (abbreviated as beta-D-LNA and alpha-L-LNA). Our findings show that the best antisense activity ...
متن کاملOligonucleotide uptake in human hematopoietic cells is increased in leukemia and is related to cellular activation.
The use of antisense oligonucleotides as tools for modulating gene expression represents a novel strategy for designing drugs to treat a variety of diseases. Several factors, including cellular uptake and internalization of the oligonucleotides, are important parameters in determining the effectiveness of antisense agents such as therapeutic drugs. We have studied oligonucleotides uptake in nor...
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تاریخ انتشار 2011