6 ms·

Not a virologist, but this seems over-hyped. There wasn't a lot of info on how DRACO works, but it seems to cause cell destruction on detection of double-strand

Not a virologist, but this seems over-hyped. There wasn't a lot of info on how DRACO works, but it seems to cause cell destruction on detection of double-stranded RNA, which means it will only work on double-stranded RNA viruses. I'm not sure how many human viral infections are caused by double-stranded RNA viruses, but from skimming the wikipedia page it doesn't seem to be many (https://en.wikipedia.org/wiki/Double-stranded_RNA_viruses https://en.wikipedia.org/wiki/Double-stranded_RNA_viruses). The main example the wiki page gives is rotaviruses, which do cause a lot of deaths of children in developing countries, but there is a vaccine available. The fact that he explicitly is saying this could treat ALL viral diseases makes me skeptical. Maybe I'm wrong, and most viruses produce dsRNA in some form or another during infection.

samch 10y ago
"Most viruses have double- or single-stranded RNA (ssRNA) genomes and produce long dsRNA helices during transcription and replication; the remainder of viruses have DNA genomes and typically produce long dsRNA via symmetrical transcription." http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0022572 http://journals.plos.org/plosone/article?id=10.1371/journal....
- openasocket 10y ago
  Ah, I missed that. But which viruses generate dsRNA? Another trip to Google gave me the following paper from the Journal of Virology: "Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses." (https://www.ncbi.nlm.nih.gov/pubmed/16641297 https://www.ncbi.nlm.nih.gov/pubmed/16641297) Assuming this paper is reputable (which I'm not really qualified to determine) that certainly seems to cover a broad category of viruses. If that paper is correct, negative strand RNA viruses (https://en.wikipedia.org/wiki/Negative-sense_single-stranded_RNA_virus https://en.wikipedia.org/wiki/Negative-sense_single-stranded...) would not be treatable with DRACO. And, according to wikipedia, that category includes Ebola, Rabies, Lassa virus and Hanta virus, which is a little disappointing. But here's the weird part. That wikipedia page also says that Influenza viruses are negative strand RNA viruses, so shouldn't produce dsRNA. But DRACO was tested against H1N1 influenza, and supposedly worked. We have a contradiction. So either the Journal of Virology paper is wrong, wikipedia is wrong is saying that Influenza is a negative strand RNA virus, or DRACO doesn't work against H1N1. Anyone care to offer some insight?
  - virusduck 10y ago
    Influenza (and other (-)ssRNA viruses) are transcribed and replicated by an RNA-dependent RNA polymerase, that is, the protein makes +RNA out of a -RNA template. This replication is happening in the cytoplasm, and for at least a limited amount of time, there is dsRNA present, although I am not sure of the on/off time for this. The paper you cite uses an antibody to detect dsRNA, which may not be an adequate marker for dsRNA ( the RNA nay be in an incompatible confirmation for the Ab, proximety to proteins may cause the RNA to be fixed to viral or other proteins during fixation procedure, etc).
    - ihnorton 10y ago
      Son (2015) shows detection of dsRNA from (-)ssRNA viruses by immunofluorescence: http://jvi.asm.org/content/89/18/9383.full http://jvi.asm.org/content/89/18/9383.full They include this comment on the Weber (2006) paper cited above: > their lack of success might relate to the production of smaller amounts of dsRNA in negative-strand RNA virus infections, the use of the less sensitive J2 MAb, the choice of less than optimum times for p.i. sampling, or, possibly, technical issues.
virusduck 10y ago
Am a virologist, and this is over-hyped, but not for that reason. The PKR/dsRNA response pathway is activated by a number of non-dsRNA viruses. There are double-stranded intermediates for lots of viruses, including herpesviruses, that we don't necessarily appreciate or know exactly how they're activated. The major issue is that these are macromolecules, and it is incredibly difficult to deliver these in vivo. Every pharmaceutical encounters this problem, and the fact that it isn't really addressed is probably why no companies are biting. There is some mouse data in the (single) paper, but it is missing some important controls. 1. He never shows that the protein makes it into the cells of the liver/kidney/lung/etc, just that there is some identifiable protein in the organs, and 2. he doesn't control for general immune activation from the injection of the protein, even though he has a control DRACO in the tissue culture experiments. Also, though it may be overkill, he never shows IFAs of the actual DRACO protein inside the cells from tissue culture.
- dogma1138 10y ago
  Will it be possible to combine this technique with genetic engineering to cause your cells to produce these proteins in the first place?
  - virusduck 10y ago
    Sure, but you still have the question of delivery mechanism in vivo, and how to target. Also, I'm not sure you'd want this produced permanently. There may be many off-target effects from over-production. Proteins that require oligomerization can be overexpressed in cells to activate them without the target present. This would be bad in an organism.

samch 10y ago

"Most viruses have double- or single-stranded RNA (ssRNA) genomes and produce long dsRNA helices during transcription and replication; the remainder of viruses have DNA genomes and typically produce long dsRNA via symmetrical transcription." http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0022572 http://journals.plos.org/plosone/article?id=10.1371/journal....

openasocket 10y ago
Ah, I missed that. But which viruses generate dsRNA? Another trip to Google gave me the following paper from the Journal of Virology: "Double-stranded RNA is produced by positive-strand RNA viruses and DNA viruses but not in detectable amounts by negative-strand RNA viruses." (https://www.ncbi.nlm.nih.gov/pubmed/16641297 https://www.ncbi.nlm.nih.gov/pubmed/16641297) Assuming this paper is reputable (which I'm not really qualified to determine) that certainly seems to cover a broad category of viruses. If that paper is correct, negative strand RNA viruses (https://en.wikipedia.org/wiki/Negative-sense_single-stranded_RNA_virus https://en.wikipedia.org/wiki/Negative-sense_single-stranded...) would not be treatable with DRACO. And, according to wikipedia, that category includes Ebola, Rabies, Lassa virus and Hanta virus, which is a little disappointing. But here's the weird part. That wikipedia page also says that Influenza viruses are negative strand RNA viruses, so shouldn't produce dsRNA. But DRACO was tested against H1N1 influenza, and supposedly worked. We have a contradiction. So either the Journal of Virology paper is wrong, wikipedia is wrong is saying that Influenza is a negative strand RNA virus, or DRACO doesn't work against H1N1. Anyone care to offer some insight?
- virusduck 10y ago
  Influenza (and other (-)ssRNA viruses) are transcribed and replicated by an RNA-dependent RNA polymerase, that is, the protein makes +RNA out of a -RNA template. This replication is happening in the cytoplasm, and for at least a limited amount of time, there is dsRNA present, although I am not sure of the on/off time for this. The paper you cite uses an antibody to detect dsRNA, which may not be an adequate marker for dsRNA ( the RNA nay be in an incompatible confirmation for the Ab, proximety to proteins may cause the RNA to be fixed to viral or other proteins during fixation procedure, etc).
  - ihnorton 10y ago
    Son (2015) shows detection of dsRNA from (-)ssRNA viruses by immunofluorescence: http://jvi.asm.org/content/89/18/9383.full http://jvi.asm.org/content/89/18/9383.full They include this comment on the Weber (2006) paper cited above: > their lack of success might relate to the production of smaller amounts of dsRNA in negative-strand RNA virus infections, the use of the less sensitive J2 MAb, the choice of less than optimum times for p.i. sampling, or, possibly, technical issues.

virusduck 10y ago

Am a virologist, and this is over-hyped, but not for that reason. The PKR/dsRNA response pathway is activated by a number of non-dsRNA viruses. There are double-stranded intermediates for lots of viruses, including herpesviruses, that we don't necessarily appreciate or know exactly how they're activated. The major issue is that these are macromolecules, and it is incredibly difficult to deliver these in vivo. Every pharmaceutical encounters this problem, and the fact that it isn't really addressed is probably why no companies are biting. There is some mouse data in the (single) paper, but it is missing some important controls. 1. He never shows that the protein makes it into the cells of the liver/kidney/lung/etc, just that there is some identifiable protein in the organs, and 2. he doesn't control for general immune activation from the injection of the protein, even though he has a control DRACO in the tissue culture experiments. Also, though it may be overkill, he never shows IFAs of the actual DRACO protein inside the cells from tissue culture.

dogma1138 10y ago
Will it be possible to combine this technique with genetic engineering to cause your cells to produce these proteins in the first place?
- virusduck 10y ago
  Sure, but you still have the question of delivery mechanism in vivo, and how to target. Also, I'm not sure you'd want this produced permanently. There may be many off-target effects from over-production. Proteins that require oligomerization can be overexpressed in cells to activate them without the target present. This would be bad in an organism.