Polyinosinic:polycytidylic acid: Difference between revisions

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{{Drugbox
{{Short description|Synthetic analog of double-stranded RNA}}
| Verifiedfields = changed
{{DISPLAYTITLE:Polyinosinic:polycytidylic acid}}
| verifiedrevid = 447996040
| IUPAC_name = poly[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate;
| image = Poly I-C structure.svg
| width = 300
| drug_name = Polyinosinic:polycytidylic acid, sodium salt
<!-- Clinical data -->
| tradename = 
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B            / C / D / X -->
| pregnancy_category = 
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA = <!--            / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL        / P      / POM / CD / Class A, B, C -->
| legal_US = <!-- OTC                  / Rx-only  / Schedule I, II, III, IV, V -->
| legal_status = 
| routes_of_administration = 
<!-- Pharmacokinetic data -->
| bioavailability = 
| protein_bound = 
| metabolism = 
| elimination_half-life = 
| excretion = 
<!-- Identifiers -->
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = none
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 24939-03-5
| ATC_prefix = L03
| ATC_suffix = AX07
| PubChem = 32744
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = 
<!-- Chemical data -->
| chemical_formula = (C<sub>10</sub>H<sub>10</sub>N<sub>4</sub>NaO<sub>7</sub>P)<sub>x</sub> • (C<sub>9</sub>H<sub>11</sub>N<sub>3</sub>NaO<sub>7</sub>P)<sub>x</sub>
| molecular_weight = 
}}
'''Polyinosinic:polycytidylic acid''' (usually abbreviated '''poly I:C''' or ''poly(I:C)''') is an [[immunostimulant]]. It is used in the form of its sodium salt to simulate [[viral infections]].<ref name="pmid15205185">{{cite journal |vauthors=Fortier ME, Kent S, Ashdown H, Poole S, Boksa P, Luheshi GN |title=The viral mimic, polyinosinic:polycytidylic acid, induces fever in rats via an interleukin-1-dependent mechanism |journal=Am. J. Physiol. Regul. Integr. Comp. Physiol. |volume=287 |issue=4 |pages=R759–66 |year=2004 |pmid=15205185 |doi=10.1152/ajpregu.00293.2004}}</ref>


Poly I:C is known to interact with toll-like receptor 3 ([[TLR3]]), which is expressed in the membrane of [[B-cells]], [[macrophages]] and [[dendritic cells]]. Poly I:C is structurally similar to [[double-stranded RNA]], which is present in some [[viruses]] and is a "natural" stimulant of [[TLR3]]. Thus, Poly I:C can be considered a [[chemical synthesis|synthetic]] [[analog (chemistry)|analog]] of double-stranded RNA and is a common tool for scientific research on the [[immune system]].<ref name="pmid26494128">{{cite journal | vauthors = Li Y, Xu XL, Zhao D, Pan LN, Huang CW, Guo LJ, Lu Q, Wang J | title = TLR3 ligand Poly IC Attenuates Reactive Astrogliosis and Improves Recovery of Rats after Focal Cerebral Ischemia | journal = CNS Neurosci Ther | volume = 21 | issue = 11 | pages = 905–13 | year = 2015 | pmid = 26494128 | pmc = 4638223 | doi = 10.1111/cns.12469 }}</ref>
'''Polyinosinic:polycytidylic acid''' (commonly abbreviated as '''poly I:C''') is a synthetic analog of [[double-stranded RNA]] (dsRNA). It is composed of a strand of [[polyinosinic acid]] and a strand of [[polycytidylic acid]], which form a double-stranded structure similar to that of viral RNA. Poly I:C is widely used in research to mimic viral infections and to study the immune response, particularly the activation of the [[innate immune system]].


==Chemistry==
==Structure and Composition==
Poly I:C is a mismatched double-stranded RNA with one strand being a [[polymer]] of [[inosinic acid]], the other a polymer of [[cytidylic acid]].
Poly I:C is a synthetic polynucleotide, consisting of two complementary strands: one made of [[inosine]] residues and the other of [[cytidine]] residues. These strands are hydrogen-bonded to form a stable double helix. The structure of poly I:C resembles that of viral dsRNA, which is recognized by the immune system as a pathogen-associated molecular pattern (PAMP).


==Variants==
==Mechanism of Action==
Optimization of physicochemical properties of poly I:C has led to generation of derivatives that have increased stability in body fluids (such as [[polyICLC]]), or reduced toxicity through reduced stability in body fluids (such as poly I:C<sub>12</sub>U).<ref>{{Cite journal|last=Naumann|first=Kai|last2=Wehner|first2=Rebekka|last3=Schwarze|first3=Anett|last4=Petzold|first4=Christiane|last5=Schmitz|first5=Marc|last6=Rohayem|first6=Jacques|date=2013-12-02|title=Activation of Dendritic Cells by the Novel Toll-Like Receptor 3 Agonist RGC100|journal=Clinical and Developmental Immunology|language=en|volume=2013|pages=283649|doi=10.1155/2013/283649|issn=1740-2522|pmc=3878805|pmid=24454470}}</ref>
Poly I:C is recognized by several pattern recognition receptors (PRRs) in the immune system, including [[Toll-like receptor 3]] (TLR3) and [[RIG-I-like receptors]] (RLRs). Upon binding to these receptors, poly I:C triggers signaling pathways that lead to the production of [[type I interferons]] and other [[cytokines]], which are crucial for antiviral defense.


==References==
===Toll-like Receptor 3===
{{reflist}}
TLR3 is an endosomal receptor that recognizes dsRNA. When poly I:C binds to TLR3, it activates the [[TRIF]]-dependent signaling pathway, leading to the activation of [[NF-κB]] and [[IRF3]], transcription factors that induce the expression of interferons and pro-inflammatory cytokines.


{{Immunostimulants}}
===RIG-I-like Receptors===
{{Portal bar|Molecular and cellular biology}}
RLRs, including [[RIG-I]] and [[MDA5]], are cytoplasmic receptors that detect viral RNA. Poly I:C is primarily recognized by MDA5, which activates the [[MAVS]] signaling pathway, resulting in the production of type I interferons.


[[Category:Immunostimulants]]
==Applications in Research==
[[Category:TLR3 agonist]]
Poly I:C is extensively used in research to study the immune response to viral infections. It serves as a model for viral dsRNA, allowing researchers to investigate the mechanisms of innate immunity and the role of interferons in antiviral defense. Poly I:C is also used in cancer research to stimulate the immune system and enhance the efficacy of [[immunotherapy]].


==Therapeutic Potential==
Due to its ability to activate the immune system, poly I:C has been explored as a potential therapeutic agent in the treatment of viral infections and cancer. It has been used in clinical trials as an adjuvant to boost the immune response in [[vaccine]]s and as a direct antiviral agent.


{{antineoplastic-drug-stub}}
==Safety and Side Effects==
{{dictionary-stub1}}
While poly I:C is a powerful immune stimulant, it can also cause significant side effects, including [[inflammation]], [[fever]], and [[cytokine release syndrome]]. These effects limit its use in clinical settings, and research is ongoing to develop safer analogs and delivery methods.
<gallery>
 
File:Poly_I-C_structure.svg|Structure of Polyinosinic:polycytidylic acid
==Related Pages==
</gallery>
* [[Double-stranded RNA]]
* [[Toll-like receptor 3]]
* [[RIG-I-like receptors]]
* [[Type I interferons]]
* [[Immunotherapy]]
 
[[Category:Immunology]]
[[Category:RNA]]
[[Category:Synthetic biology]]

Latest revision as of 19:06, 22 March 2025

Synthetic analog of double-stranded RNA



Polyinosinic:polycytidylic acid (commonly abbreviated as poly I:C) is a synthetic analog of double-stranded RNA (dsRNA). It is composed of a strand of polyinosinic acid and a strand of polycytidylic acid, which form a double-stranded structure similar to that of viral RNA. Poly I:C is widely used in research to mimic viral infections and to study the immune response, particularly the activation of the innate immune system.

Structure and Composition[edit]

Poly I:C is a synthetic polynucleotide, consisting of two complementary strands: one made of inosine residues and the other of cytidine residues. These strands are hydrogen-bonded to form a stable double helix. The structure of poly I:C resembles that of viral dsRNA, which is recognized by the immune system as a pathogen-associated molecular pattern (PAMP).

Mechanism of Action[edit]

Poly I:C is recognized by several pattern recognition receptors (PRRs) in the immune system, including Toll-like receptor 3 (TLR3) and RIG-I-like receptors (RLRs). Upon binding to these receptors, poly I:C triggers signaling pathways that lead to the production of type I interferons and other cytokines, which are crucial for antiviral defense.

Toll-like Receptor 3[edit]

TLR3 is an endosomal receptor that recognizes dsRNA. When poly I:C binds to TLR3, it activates the TRIF-dependent signaling pathway, leading to the activation of NF-κB and IRF3, transcription factors that induce the expression of interferons and pro-inflammatory cytokines.

RIG-I-like Receptors[edit]

RLRs, including RIG-I and MDA5, are cytoplasmic receptors that detect viral RNA. Poly I:C is primarily recognized by MDA5, which activates the MAVS signaling pathway, resulting in the production of type I interferons.

Applications in Research[edit]

Poly I:C is extensively used in research to study the immune response to viral infections. It serves as a model for viral dsRNA, allowing researchers to investigate the mechanisms of innate immunity and the role of interferons in antiviral defense. Poly I:C is also used in cancer research to stimulate the immune system and enhance the efficacy of immunotherapy.

Therapeutic Potential[edit]

Due to its ability to activate the immune system, poly I:C has been explored as a potential therapeutic agent in the treatment of viral infections and cancer. It has been used in clinical trials as an adjuvant to boost the immune response in vaccines and as a direct antiviral agent.

Safety and Side Effects[edit]

While poly I:C is a powerful immune stimulant, it can also cause significant side effects, including inflammation, fever, and cytokine release syndrome. These effects limit its use in clinical settings, and research is ongoing to develop safer analogs and delivery methods.

Related Pages[edit]

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