Ranpirnase is a
ribonuclease
Ribonuclease (commonly abbreviated RNase) is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonucleases can be divided into endoribonucleases and exoribonucleases, and comprise several sub-classes within the ...
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
found in the
oocytes
An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ge ...
of the
Northern Leopard Frog
''Lithobates pipiens''Integrated Taxonomic Information System nternet2012''Lithobates pipiens'' pdated 2012 Sept; cited 2012 Dec 26Available from: www.itis.gov/ or ''Rana pipiens'', commonly known as the northern leopard frog, is a species of le ...
(''Rana pipiens''). Ranpirnase is a member of the
pancreatic ribonuclease
Pancreatic ribonuclease family (, ''RNase'', ''RNase I'', ''RNase A'', ''pancreatic RNase'', ''ribonuclease I'', ''endoribonuclease I'', ''ribonucleic phosphatase'', ''alkaline ribonuclease'', ''ribonuclease'', ''gene S glycoproteins'', ''Ceratit ...
(RNase A) protein superfamily and degrades
RNA
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
substrates with a
sequence
In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is calle ...
preference for
uracil
Uracil () (symbol U or Ura) is one of the four nucleobases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by ...
and
guanine
Guanine () ( symbol G or Gua) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine (uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside is called ...
nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...
s. Along with
amphinase
Amphinase is a ribonuclease enzyme found in the oocytes of the Northern leopard frog ''(Rana pipiens)''. Amphinase is a member of the pancreatic ribonuclease protein superfamily and degrades long RNA substrates. Along with ranpirnase, another leo ...
, another leopard frog ribonuclease, Ranpirnase has been studied as a potential
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
and antiviral treatment due to its unusual mechanism of
cytotoxicity
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa'').
Cell physiology
Treating cells ...
tested against
transformed cells and antiviral activity.
Ranpirnase was originally discovered by scientists at TamirBio, a
biotechnology
Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used b ...
company (formerly Alfacell Corporation), where it was tested in preclinical assays
and in
clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
s under the name ''Pannon'' or ''Onconase'', and ''TMR004''. The
mechanism of action
In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targe ...
of ranpirnase has been attributed to the
RNA interference
RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by o ...
pathway, potentially through cleaving
siRNA
Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA at first non-coding RNA molecules, typically 20-24 (normally 21) base pairs in length, similar to miRNA, and operating wi ...
molecules;
to cleavage of
transfer RNA
Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino ac ...
;
and to interference with the
NF-κB
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...
pathway. Currently (as of March 2020) Ranpirnase is in clinical trials as a potential antiviral.
References
Ribonucleases
Experimental drugs
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