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curecomingverysoon

Antagomirs

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curecomingverysoon

This is for anyone who has read the Duke University research and has wondered what an antagomir is and how it operates. If anyone wants to expand on this, that would be great.

The wikipedia stub says:

Antagomirs are one of a novel class of chemically engineered oligonucleotides. Antagomirs are used to silence endogenous microRNA.[1][2]

An antagomir is a small synthetic RNA that is perfectly complementarity to the specific miRNA target with either mispairing at the cleavage site of Ago2 or some sort of base modification to inhibit Ago2 cleavage.. Usually, antagomirs has some sort of modification to make it more resistant to degradation . It is unclear how antagomirization (the process by which an antagomir inhibits miRNA activity), but it is believe to inhibit by irreversibly binding the miRNA.

References

^ Krützfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M. (December 2005). "Silencing of microRNAs in vivo with 'antagomirs'". Nature 438 (7068): 685–9. doi:10.1038/nature04303. PMID : 16258535. http://www.nature.com/doifinder/10.1038/nature04303

^ Czech Michael P (2006). "MicroRNAs as Therapeutic Targets". New England Journal of Medicine 354 (11): 2. doi:10.1056/NEJMcibr060065. PMID 16540623. http://content.nejm.org/cgi/content/extract/354/11/1194

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unheardof

It sounds like a very specific and technical variation of RNAi, which is a relatively new technique of silencing gene expression. I'll try to give an overview of RNAi as well as I understand it.

Generally, RNAi doesn't completely turn off a gene, but rather it tones it down so that it's only partially expressed. This is one of the challenges with using the technique. The whole process works based on the physical structure of DNA. DNA is just a series of building blocks called nucleotides. There are actually only four different types of nucleotides, and each one is represented by a letter. So, DNA can be "read" by making a series of these letters. Anyway, normally a body uses DNA by "reading" its message. First, it translates it into RNA, and the RNA is then "read" and translated into into proteins and other essential components of our bodies. DNA has two strands, or a "double helix" structure, while RNA normally has only one strand. RNAi interferes with this whole process at the RNA level. Scientists have learned how to create very specific RNA pieces that will bind with normal RNA to make it double stranded. Double stranded RNA is sometimes found in viruses, but not in humans. We have a natural immune response to dice up double stranded RNA to get rid of viruses. So, RNAi can knock down gene expression by forming these double stranded RNA pieces and taking advantage of this immune response. If the double stranded RNA happen to belong to a virus, say HSV, then we're getting somewhere. The trouble is, RNAi doesn't completely silence genes, and we often don't know what genes are important to silence in the first place. Also, with only four letters in the DNA alphabet, it's tough to figure out how to silence HSV genes without affecting a similar piece of RNA that belongs to us! We've come a long way with this method in the past few years, and it seems to be a really promising way to develop vaccines and cures.

In terms of RNAi applications for HSV, it seems that HSV activation has to do with miRNA. Altering the expression of these RNAs with RNAi might be a way to either prevent HSV from ever activating OR to keep HSV from hiding in the first place (a CURE!) Cross your fingers!

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Ultra Violet

Well I still didn't understand it but thanks for trying ;) Fingers firmly crossed!

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unheardof

Haha okay, sorry. If anyone wants to know about RNAi in depth, there is a good wikipedia article on it. Otherwise, here's my attempt at a basic explanation:

RNA Interference, or RNAi, is a natural process in the body. One of its uses is an immune response to viruses. Our bodies are able to recognize a unique component of viruses and render it useless through a process that is still not completely understood. However, scientists have learned how to take advantage of this natural process to alter the way our bodies normally express genes. Also, they are working on ways to use this process to create vaccines and/or cures for viral diseases such as HSV, but there are many ways in which the process can be potentially dangerous or simply difficult.

Antagomirs seem to be one of the components of RNAi, or possibly one specific version of RNAi that is performed in labs.

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