Miravirsen (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway. Before the advent of motorized transportation, they also provided accomm ...

; codenamed SPC3649) is an experimental drug for the treatment of

hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection period, people often have mild or no symptoms. Early symptoms can include ...

, being developed by Santaris Pharma. As of 2017 it was in Phase II clinical trials. Miravirsen had been given by

subcutaneous injection Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion. A subcutaneous injection is administered as a bolus (medicine), bolus into the subcutis, the layer of skin directly below the dermis and ...

in early clinical trials as of 2017. It is

antisense In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context, ...

to a human

microRNA Micro ribonucleic acid (microRNA, miRNA, μRNA) are small, single-stranded, non-coding RNA molecules containing 21–23 nucleotides. Found in plants, animals, and even some viruses, miRNAs are involved in RNA silencing and post-transcr ...

called

miR-122 miR-122 is a miRNA that is conserved among vertebrate species. miR-122 is not present in invertebrates, and no close paralogs of miR-122 have been detected. miR-122 is highly expressed in the liver, where it has been implicated as a regulator of ...

. miR-122 ferries an

argonaute The Argonaute protein family, first discovered for its evolutionarily conserved stem cell function, plays a central role in RNA silencing processes as essential components of the RNA-induced silencing complex (RISC). RISC is responsible for the ...

protein to 5'-UTR region of viral RNA, where it binds, protecting the RNA from being destroyed by normally present

nuclease In biochemistry, a nuclease (also archaically known as nucleodepolymerase or polynucleotidase) is an enzyme capable of cleaving the phosphodiester bonds that link nucleotides together to form nucleic acids. Nucleases variously affect single and ...

s; by binding to miR-122, miravirsen removes that protection and the virus RNA can be destroyed. There is some evidence that the 5'-UTR region mutates under repeated exposure to miravirsen. Miravirsen is a modified

oligonucleotide Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, Recombinant DNA, research, and Forensic DNA, forensics. Commonly made in the laboratory by Oligonucleotide synthesis, solid-phase ...

consisting of a chain of 15

nucleotide Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...

s, the base sequence of which is designed to selectively bind to miR-122. Seven of the 15 sugar units are

deoxyribose Deoxyribose, or more precisely 2-deoxyribose, is a monosaccharide with idealized formula H−(C=O)−(CH2)−(CHOH)3−H. Its name indicates that it is a deoxy sugar, meaning that it is derived from the sugar ribose by loss of a hydroxy group. D ...

s, and the other eight are

ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally occurring form, , is a component of the ribonucleotides from which RNA is built, and so this comp ...

s with an additional bridge between the 2' oxygen and the 4' carbon atoms; this makes the molecule a

locked nucleic acid A locked nucleic acid (LNA), also known as bridged nucleic acid (BNA), and often referred to as inaccessible RNA, is a modified RNA nucleotide in which the ribose moiety is modified with an extra bridge connecting the 2' oxygen and 4' carbon. The ...

. Furthermore, the phosphate units have been replaced by

thiophosphate Thiophosphates (or phosphorothioates, PS) are chemical compounds and anions with the general chemical formula (''x'' = 0, 1, 2, or 3) and related derivatives where organic groups are attached to one or more O or S. Thiophosphates feature tetrahedr ...

s. The complete base sequence is : mC*-d C- A*-d T-dT- G*- mU*-dC-dA-mC*-dA-mC*-dT-mC*-mC* code>d = 2'-deoxy, m = 5-methyl, * = 2'-O,4'-C-methylene, i.e. bridged or "locked" sugarwith 3'→5' thiophosphate linkages. File:LNASchem.svg , Chemical structure of a single

nucleoside Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotid ...

(sugar plus base) of a

References

{{reflist Anti–hepatitis C agents Antisense RNA