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Polyinosinic-polycytidylic acid

Vaxjo ID 296       
Vaccine Adjuvant Name Polyinosinic-polycytidylic acid       
Alternative Names poly I:C, or PIC       
Adjuvant VO ID VO_0005661
Description Poly I:C is a synthetic double-stranded RNA composed of polyinosinic acid and polycytidylic acid that mimics viral RNA and activates innate immune responses.       
Stage of Development Research       
Host Species for Testing Mouse       
Components Polyinosinic-polycytidylic acid (PIC), a double-stranded RNA that induces innate immunity in mammals       
Structure It is a stable double-stranded helix formed by the hybridization of homopolymers poly-I and poly-C.       
Appearance Poly I:C appears as a colorless or slightly opalescent aqueous solution.       
Storage Stable in PBS and stored at 25°C or 40°C for up to 4 months; long-term storage at 5°C is suggested for enhanced stability.       
Preparation Synthesized enzymatically by PNPase, followed by annealing of poly-I and poly-C strands under controlled temperature and pH.       
Dosage In mouse models, doses ranged from 0.1–1 µg per well or 1 mg/kg body weight depending on the application.       
Function The potency and adverse effects of PIC are strongly correlated with the nucleotide length, and the inability to precisely control the length in PIC production limits its practical use. Length extension during the annealing process is the major factor underlying the lack of control, but tuning the annealing conditions is insufficient to resolve this issue. In this study, we developed a novel method to produce accurate nucleotide length PIC at an industrial scale. The length extension was significantly suppressed by the assembly of multiple short polyinosinic acid molecules with one long polycytidylic acid molecule. A newly developed PIC, uPIC100-400, demonstrated a reproducible length and better storage stability than that of corresponding evenly structured PIC. Human dsRNA receptors exhibited equivalent responsiveness to uPIC100-400 and the evenly structured PIC with the same length       
Safety Poly I:C is immunostimulatory but may cause dose-dependent adverse effects such as inflammation, especially at high concentrations.       
References
Nakano et al., 2018: Nakano T, Yamamura ET, Fujita H, Sone T, Asano K. Novel methods for nucleotide length control in double-stranded polyinosinic-polycytidylic acid production using uneven length components. Bioscience, biotechnology, and biochemistry. 2018; 82(11); 1889-1901. [PubMed: 30079840].