Abstract
Aptamers are oligonucleotides that can bind to various nonnucleic acid molecular targets in a high affinity and specificity. As an emerging class of therapeutic agents, aptamers offer an unparalleled advantage over other classes of therapeutic agents: the possibility to rationally regulate the therapeutic activity of aptamers. Most existing strategies for regulating the aptamer activity have a limited specificity and/or reversibility. Herein we report a simple, generic strategy to simultaneously achieve specificity and reversibility by exploiting the spontaneous conformational change of hairpin oligonucleotides upon the specific recognition of nucleic acid effectors. The effector-responsive hairpin oligonucleotide consists of a sensing loop that recognizes a particular nucleic acid effector, an aptamer stem that inhibits a certain therapeutic target, and an antidote stem that is complementary to the aptamer. Upon the introduction/removal of the effector, the hairpin oligonucleotide undergoes a conformational change that activates/deactivates the aptamer's inhibiting activity on the therapeutic target. This new strategy has been demonstrated with an anticoagulant aptamer that binds and inhibits human α-thrombin.
| Original language | English |
|---|---|
| Pages (from-to) | 77-84 |
| Number of pages | 8 |
| Journal | Journal of laboratory automation |
| Volume | 18 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jun 3 2013 |
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Keywords
- Antidotes
- Aptamers
- Hairpin oligonucleotides
- Nucleic acid effectors
- Reversible anticoagulant
ASJC Scopus subject areas
- Computer Science Applications
- Medical Laboratory Technology
Cite this
Reversible regulation of aptamer activity with effector-responsive hairpin oligonucleotides. / Li, Na.
In: Journal of laboratory automation, Vol. 18, No. 1, 03.06.2013, p. 77-84.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reversible regulation of aptamer activity with effector-responsive hairpin oligonucleotides
AU - Li, Na
PY - 2013/6/3
Y1 - 2013/6/3
N2 - Aptamers are oligonucleotides that can bind to various nonnucleic acid molecular targets in a high affinity and specificity. As an emerging class of therapeutic agents, aptamers offer an unparalleled advantage over other classes of therapeutic agents: the possibility to rationally regulate the therapeutic activity of aptamers. Most existing strategies for regulating the aptamer activity have a limited specificity and/or reversibility. Herein we report a simple, generic strategy to simultaneously achieve specificity and reversibility by exploiting the spontaneous conformational change of hairpin oligonucleotides upon the specific recognition of nucleic acid effectors. The effector-responsive hairpin oligonucleotide consists of a sensing loop that recognizes a particular nucleic acid effector, an aptamer stem that inhibits a certain therapeutic target, and an antidote stem that is complementary to the aptamer. Upon the introduction/removal of the effector, the hairpin oligonucleotide undergoes a conformational change that activates/deactivates the aptamer's inhibiting activity on the therapeutic target. This new strategy has been demonstrated with an anticoagulant aptamer that binds and inhibits human α-thrombin.
AB - Aptamers are oligonucleotides that can bind to various nonnucleic acid molecular targets in a high affinity and specificity. As an emerging class of therapeutic agents, aptamers offer an unparalleled advantage over other classes of therapeutic agents: the possibility to rationally regulate the therapeutic activity of aptamers. Most existing strategies for regulating the aptamer activity have a limited specificity and/or reversibility. Herein we report a simple, generic strategy to simultaneously achieve specificity and reversibility by exploiting the spontaneous conformational change of hairpin oligonucleotides upon the specific recognition of nucleic acid effectors. The effector-responsive hairpin oligonucleotide consists of a sensing loop that recognizes a particular nucleic acid effector, an aptamer stem that inhibits a certain therapeutic target, and an antidote stem that is complementary to the aptamer. Upon the introduction/removal of the effector, the hairpin oligonucleotide undergoes a conformational change that activates/deactivates the aptamer's inhibiting activity on the therapeutic target. This new strategy has been demonstrated with an anticoagulant aptamer that binds and inhibits human α-thrombin.
KW - Antidotes
KW - Aptamers
KW - Hairpin oligonucleotides
KW - Nucleic acid effectors
KW - Reversible anticoagulant
UR - http://www.scopus.com/inward/record.url?scp=84878299398&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878299398&partnerID=8YFLogxK
U2 - 10.1177/2211068212448429
DO - 10.1177/2211068212448429
M3 - Article
C2 - 22651934
AN - SCOPUS:84878299398
VL - 18
SP - 77
EP - 84
JO - JALA - Journal of the Association for Laboratory Automation
JF - JALA - Journal of the Association for Laboratory Automation
SN - 2211-0682
IS - 1
ER -