3 ms·

> Mark Connors, the lead NIH scientist who discovered the N6 antibody, was among the viewers. > Connors was unimpressed with the scientific reasoning behind th

> Mark Connors, the lead NIH scientist who discovered the N6 antibody, was among the viewers. > Connors was unimpressed with the scientific reasoning behind the treatment. "These seem like very smart young men and they have command of some of the facts, but not all the facts," he said. > "For the most part, the rules aren't what take so long [in drug development]," he added. "It's not the FDA sitting on drugs. The reality is this is a deliberative process."

toufka 9y ago
It's curious, the hard 'scientific' challenge is finding the N6 antibody sequence. That code/blueprint produces the atomically-precise nanomachine that is capable of neutralizing HIV. That work is done. Here it is: >RAHLVQSGTAMKKPGASVRVSCQTSGYTFTAHILFWFRQAPGRGLEWVGWIKPQYGAVNFGGGFRDRVTLTRDVYREIAYMDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVVVSA [1] [2] Yet the current, engineering-style challenge is getting that protein sequence expressed in the right place, at the right time, without disturbing its environment, etc. It's hard to compare the difficulty or danger of trying a therapy with 'scientific' risks versus 'engineering' risks. At first glance it might appear that now that the scientific problem has been solved (to a particular extent), that the engineering challenge is easy. However, the details really do matter. And not having all the facts, can in fact be lethal. On the other hand, to some extent, the scientific challenge really is the limiting capability, whereas the engineering challenge could be considered one of degree and risk. One this guy, for better or worse, was willing to take. [1] https://www.ncbi.nlm.nih.gov/protein/1079417984 https://www.ncbi.nlm.nih.gov/protein/1079417984 [2] http://www.cell.com/immunity/fulltext/S1074-7613(16)30438-1 http://www.cell.com/immunity/fulltext/S1074-7613(16)30438-1
- fabian2k 9y ago
  I was a bit confused until I noticed that this is only a partial sequence. A full antibody is considerably larger, and you also need to get the disulfide bonds formed correctly for it to work. And I don't think it is entirely clear if expressing that antibody alone is enough to defeat HIV, especially as it targets the immune system itself. If antibodies are the solution, then developing a vaccine that triggers the production of suitable antibodies is probably the better way forward.
  - toufka 9y ago
    Yep. It's just the heavy chain. If it's expressed in vivo (in the right place) it should form properly. And N6 isn't a full cure, but it has shown therapeutic benefit. Details do matter, but the general idea still stands. The vaccines that trigger antibody production actually are being made.
- klmr 9y ago
  You’re exactly right. What I don’t see is how Roberts’ experiments help advancing that engineering challenge; the article gave no details about the injection, such as the vector being used to get the genetic material into cells, or the carrier, etc.
- carbocation 9y ago
  > It's curious, the hard 'scientific' challenge is finding the N6 antibody sequence. The discoverer of N6 doesn't seem to agree: > As potent as N6 is, HIV can still develop a resistance to it, making it a poor candidate as a "monotherapy" or stand-alone treatment, said Connors. If Connors is right, finding the N6 sequence alone, and in fact even delivering a functional N6 with a perfectly safe and effective vector, probably isn't adequate. Given the genomic integration of HIV, that's no surprise.

toufka 9y ago

It's curious, the hard 'scientific' challenge is finding the N6 antibody sequence. That code/blueprint produces the atomically-precise nanomachine that is capable of neutralizing HIV. That work is done. Here it is: >RAHLVQSGTAMKKPGASVRVSCQTSGYTFTAHILFWFRQAPGRGLEWVGWIKPQYGAVNFGGGFRDRVTLTRDVYREIAYMDIRGLKPDDTAVYYCARDRSYGDSSWALDAWGQGTTVVVSA [1] [2] Yet the current, engineering-style challenge is getting that protein sequence expressed in the right place, at the right time, without disturbing its environment, etc. It's hard to compare the difficulty or danger of trying a therapy with 'scientific' risks versus 'engineering' risks. At first glance it might appear that now that the scientific problem has been solved (to a particular extent), that the engineering challenge is easy. However, the details really do matter. And not having all the facts, can in fact be lethal. On the other hand, to some extent, the scientific challenge really is the limiting capability, whereas the engineering challenge could be considered one of degree and risk. One this guy, for better or worse, was willing to take. [1] https://www.ncbi.nlm.nih.gov/protein/1079417984 https://www.ncbi.nlm.nih.gov/protein/1079417984 [2] http://www.cell.com/immunity/fulltext/S1074-7613(16)30438-1 http://www.cell.com/immunity/fulltext/S1074-7613(16)30438-1

fabian2k 9y ago
I was a bit confused until I noticed that this is only a partial sequence. A full antibody is considerably larger, and you also need to get the disulfide bonds formed correctly for it to work. And I don't think it is entirely clear if expressing that antibody alone is enough to defeat HIV, especially as it targets the immune system itself. If antibodies are the solution, then developing a vaccine that triggers the production of suitable antibodies is probably the better way forward.
- toufka 9y ago
  Yep. It's just the heavy chain. If it's expressed in vivo (in the right place) it should form properly. And N6 isn't a full cure, but it has shown therapeutic benefit. Details do matter, but the general idea still stands. The vaccines that trigger antibody production actually are being made.
klmr 9y ago
You’re exactly right. What I don’t see is how Roberts’ experiments help advancing that engineering challenge; the article gave no details about the injection, such as the vector being used to get the genetic material into cells, or the carrier, etc.
carbocation 9y ago
> It's curious, the hard 'scientific' challenge is finding the N6 antibody sequence. The discoverer of N6 doesn't seem to agree: > As potent as N6 is, HIV can still develop a resistance to it, making it a poor candidate as a "monotherapy" or stand-alone treatment, said Connors. If Connors is right, finding the N6 sequence alone, and in fact even delivering a functional N6 with a perfectly safe and effective vector, probably isn't adequate. Given the genomic integration of HIV, that's no surprise.