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Branched RNA: A New Architecture for RNA Interference.

Aviñó A, Ocampo SM, Perales JC, Eritja R - J Nucleic Acids (2011)

Bottom Line: These structures were used to obtain branched siRNA.Branched RNAs are considered novel structures for siRNA technology, and they provide an innovative tool for specific gene inhibition.As the method described here is compatible with most RNA modifications described to date, these compounds may be further functionalized to obtain more potent siRNA derivatives and can be attached to suitable delivery systems.

View Article: PubMed Central - PubMed

Affiliation: Institute for Research in Biomedicine (IRB Barcelona), Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), Networking Centre on Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), Baldiri Reixac 10, 08028 Barcelona, Spain.

ABSTRACT
Branched RNAs with two and four strands were synthesized. These structures were used to obtain branched siRNA. The branched siRNA duplexes had similar inhibitory capacity as those of unmodified siRNA duplexes, as deduced from gene silencing experiments of the TNF-α protein. Branched RNAs are considered novel structures for siRNA technology, and they provide an innovative tool for specific gene inhibition. As the method described here is compatible with most RNA modifications described to date, these compounds may be further functionalized to obtain more potent siRNA derivatives and can be attached to suitable delivery systems.

No MeSH data available.


Duplex RNA architectures for RNA interference. (a) Described previously in the introduction: (i) canonical siRNA antiparallel duplex; (ii) small internally segmented interfering RNA (sisiRNA); (iii) small hairpin RNA (shRNA); (iv) dumbbell siRNA. (b) Branched siRNA described in this study: (v) four-stranded RNA; (vi) two-stranded RNA.
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fig1: Duplex RNA architectures for RNA interference. (a) Described previously in the introduction: (i) canonical siRNA antiparallel duplex; (ii) small internally segmented interfering RNA (sisiRNA); (iii) small hairpin RNA (shRNA); (iv) dumbbell siRNA. (b) Branched siRNA described in this study: (v) four-stranded RNA; (vi) two-stranded RNA.

Mentions: In addition to these modifications, siRNA architecture is also crucial in the design of effective and specific siRNA. The architecture itself can be altered by chemical synthesis. In addition to the canonical siRNA architecture of 21-nt antiparallel, double-strand RNA with 2-nt 3′-overhangs [12], several forms of siRNA have been described. Blunt-ended siRNA [13], 25/27 mer Dicer-substrate or asymmetric siRNA [14] are among the siRNA structures formed by two strands. Moreover, functional siRNA can also be formed by one single RNA strand. This is the case in small hairpin RNA (shRNA), where the two strands are linked by a single loop [15], or RNA dumbbells [16], made by closing the open end of the hairpin. This last structure retains RNAi activity while providing complete protection from nucleases [16]. Finally, siRNA can also comprise three strands, namely, two 9–13 nt sense strands and the intact antisense strand. This structure is known as small internally segmented interfering RNA [17] (sisiRNA). Some of these modifications have reduced off-target effects and increased potency (Figure 1(a)). Another architecture not yet explored in siRNA is the branched RNA structure obtained from a central building unit and several branching points that enable the strand growth.


Branched RNA: A New Architecture for RNA Interference.

Aviñó A, Ocampo SM, Perales JC, Eritja R - J Nucleic Acids (2011)

Duplex RNA architectures for RNA interference. (a) Described previously in the introduction: (i) canonical siRNA antiparallel duplex; (ii) small internally segmented interfering RNA (sisiRNA); (iii) small hairpin RNA (shRNA); (iv) dumbbell siRNA. (b) Branched siRNA described in this study: (v) four-stranded RNA; (vi) two-stranded RNA.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3065013&req=5

fig1: Duplex RNA architectures for RNA interference. (a) Described previously in the introduction: (i) canonical siRNA antiparallel duplex; (ii) small internally segmented interfering RNA (sisiRNA); (iii) small hairpin RNA (shRNA); (iv) dumbbell siRNA. (b) Branched siRNA described in this study: (v) four-stranded RNA; (vi) two-stranded RNA.
Mentions: In addition to these modifications, siRNA architecture is also crucial in the design of effective and specific siRNA. The architecture itself can be altered by chemical synthesis. In addition to the canonical siRNA architecture of 21-nt antiparallel, double-strand RNA with 2-nt 3′-overhangs [12], several forms of siRNA have been described. Blunt-ended siRNA [13], 25/27 mer Dicer-substrate or asymmetric siRNA [14] are among the siRNA structures formed by two strands. Moreover, functional siRNA can also be formed by one single RNA strand. This is the case in small hairpin RNA (shRNA), where the two strands are linked by a single loop [15], or RNA dumbbells [16], made by closing the open end of the hairpin. This last structure retains RNAi activity while providing complete protection from nucleases [16]. Finally, siRNA can also comprise three strands, namely, two 9–13 nt sense strands and the intact antisense strand. This structure is known as small internally segmented interfering RNA [17] (sisiRNA). Some of these modifications have reduced off-target effects and increased potency (Figure 1(a)). Another architecture not yet explored in siRNA is the branched RNA structure obtained from a central building unit and several branching points that enable the strand growth.

Bottom Line: These structures were used to obtain branched siRNA.Branched RNAs are considered novel structures for siRNA technology, and they provide an innovative tool for specific gene inhibition.As the method described here is compatible with most RNA modifications described to date, these compounds may be further functionalized to obtain more potent siRNA derivatives and can be attached to suitable delivery systems.

View Article: PubMed Central - PubMed

Affiliation: Institute for Research in Biomedicine (IRB Barcelona), Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), Networking Centre on Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), Baldiri Reixac 10, 08028 Barcelona, Spain.

ABSTRACT
Branched RNAs with two and four strands were synthesized. These structures were used to obtain branched siRNA. The branched siRNA duplexes had similar inhibitory capacity as those of unmodified siRNA duplexes, as deduced from gene silencing experiments of the TNF-α protein. Branched RNAs are considered novel structures for siRNA technology, and they provide an innovative tool for specific gene inhibition. As the method described here is compatible with most RNA modifications described to date, these compounds may be further functionalized to obtain more potent siRNA derivatives and can be attached to suitable delivery systems.

No MeSH data available.