1993
DOI: 10.1089/ard.1993.3.339
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Abstract: To assess the usefulness of computer-assisted modeling of mRNA as an aid in design of antisense DNA, the efficiency of inhibition of translation of rabbit beta-globin mRNA by various antisense sequences was compared with calculated structures of the mRNA. The model obtained by consideration of 30 lowest-energy computer-simulated structures is consistent with the high accessibility of the AUG initiation codon region known from digestion with nucleases and with previous antisense inhibition studies reported in t… Show more

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Cited by 24 publications
(11 citation statements)
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“…The simplest approach is one in which the minimum free energy structure predicted by mfold or a similar algorithm is used to select antisense sequences complementary to singlestranded regions. An extension of this approach was applied by Jaroszewski et al (1993), who considered the 30 lowest free energy structures of RBG mRNA as an ensemble and identified those bases that were least likely to form intramolecular basepairs. The effectiveness of phosphorothioate *All energies in kcal/mole.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…The simplest approach is one in which the minimum free energy structure predicted by mfold or a similar algorithm is used to select antisense sequences complementary to singlestranded regions. An extension of this approach was applied by Jaroszewski et al (1993), who considered the 30 lowest free energy structures of RBG mRNA as an ensemble and identified those bases that were least likely to form intramolecular basepairs. The effectiveness of phosphorothioate *All energies in kcal/mole.…”
Section: Discussionmentioning
confidence: 99%
“…Also, this method of selection could also result in molecules which achieve their action nonspecifically, e.g., by acting through a tetra-guanine structural motif (Tsiang et al, 1995). Predictions of RNA folding structures have been used in design strategies that are based on finding locations on the mRNA predicted to be single-stranded and, presumably, accessible to oligonucleotide binding (Jaroszewski et al, 1993;Sczakiel et al, 1993). However, it has been shown that regions predicted to be double-stranded are, in some instances, more susceptible targets for antisense inhibition than single-stranded regions (Laptev et al, 1994;Ho et al, 1998).…”
Section: Introductionmentioning
confidence: 99%
“…Another "data poor" limitation in our study and related research [ 6 , 17 , 29 ] is that not all possible target RNA structures are taken into account. As pointed out by Mathews, an ideal way to integrate the predicted RNA structures would be to compute a partition function, which sums the contributions of all structures weighted by their Boltzmann probabilities [ 44 ].…”
Section: Discussionmentioning
confidence: 98%
“…Studies on ensembles of target structures in ODNs design date back to Jaroszewski et al . [ 29 ], who considered the 30 lowest-energy computer-simulated structures of rabbit β -globin mRNA qualitatively. In some thermodynamic models, multiple predicted target structures have been merged into the form of free energy [ 30 , 31 ].…”
Section: Introductionmentioning
confidence: 99%
“…Several S-ODN target sequences were chosen around the start codon, because this area is known for its strong 'antisense-activity' [21]. The presence of 'activity-enhancing sequence motifs' [22] and predicted stabilities of anti-senseoligonucleotide/target mRNA duplexes [23] were also considered for S-ODN design.…”
Section: Design Of Different Cd55-and Cd46-specific Anti-sense Oligonmentioning
confidence: 99%