4 ms·

How exactly do you edit a gene? Like, it is very, very small thing. How do you even measure it, let alone replace it?

by wheelerof4te 4y ago

xen2xen1 4y ago
Viruses do that an astounding number of times a day, every day, don't they? And this treatment uses a virus.
- yCombLinks 4y ago
  A virus that we've modified to deliver the genetic payload we want inserted at a specific point in this child's DNA. It's not "give this child a random virus we have laying around, that'll fix her".
yazaddaruvala 4y ago
Keywords to search for "CRISPR Cas9"
bglazer 4y ago
Biochemistry is wild! Measuring is an absolutely fascinating procedure. The predominant method is called sequencing by synthesis. Illumina is the company that basically rules the market for this technology, they have some decent explanatory videos if you’re interested. The first steps are to isolate DNA, then break it into small bits, replicate those small pieces thousands of times, and then anchor these to a glass slide. Then flow a solution over the slide with the individual DNA bases (ATCG) that have been modified to fluoresce when illuminated with a certain wavelength of light. These fluorescently labeled nucleotides get assembled one by one into strands that match the small fragments from the DNA sample. Each time the fluorescent DNA bases are added a laser is shined on the glass slide and a very sensitive microscope camera reads how many strands shone at the frequency that corresponds to A T C and G. This tells you which base just got added to which strand. Repeat a couple hundred times and you have a huge number of sequences of ATCG’s corresponding to each short strand of DNA in the sample. The problem now is assembling these short sequences into a full genome. Basically, the puzzle is finding the arrangement of short sequences that maximizes the overlap between them and their agreement with a reference genome. It’s a pretty interesting problem that (I believe) is classically solved with dynamic programming, although I don’t know the most recent methods. I really don’t think it’s well enough appreciated how integral computation is to DNA sequencing. Signal processing in the camera, assembling the genome fragments, determining whether a mutation exists, and all the subsequent analysis to give biological meaning to a sequence. Edit: editing is a whole other, extremely complicated procedure. In fact, direct editing isn’t really possible now. Instead we can basically just delete and insert.
- aaauaucuggaa 4y ago
  Your answer is much better
- ruskyhacker 4y ago
  Thank you for the detailed explanation!
- syastrov 4y ago
  It is super interesting! I was at a talk where a genetics company used the Smith-Waterman algorithm (1) to perform sequence alignment. Still I believe it took a long time (24 hours?) to perform the calculations. They were working on optimizing the code as doing so could mean a faster turnaround. 1. https://en.m.wikipedia.org/wiki/Smith–Waterman_algorithm https://en.m.wikipedia.org/wiki/Smith–Waterman_algorithm
- wheelerof4te 4y ago
  Thank you very much for the detailed explanation. This is the kind of content I visit this site for.
aaauaucuggaa 4y ago
With DNA sequencing?
- l33t233372 4y ago
  I believe the question could be more thoroughly phrased as “How does DNA sequencing work with such precision at such scales that we can edit DNA?” This formulation has the added benefit of not being easily answered with a flippant remark.
raffraffraff 4y ago
Vim or Emacs. But vim is better.
- flir 4y ago
  Yeah, if you want DNA littered with ESC, CTRL+c, CTRL+z, CMD+q, CMD+w, ALT+F4... Don't take the chance, people. Edit your DNA with notepad.
  - raffraffraff 4y ago
    Noooo! Then you'll have ^M on each line!
- ta1243 4y ago
  Real molecular biologists use butterflys...
refurb 4y ago
Its similar to chemistry. You cant see molecules. We have a set of tools that let you determine biological structures (sometimes entirely, sometimes only partially). We also have a set of tools to modify genes. Some viruses already do this, so we use them. Were also using CRISPR which is based on the machinery of bacteria. So you use the modification tools to change genes and the analytical tools to prove you did it correctly. Of course the level of complexity is way higher since your dealing with a living organism and the modification tools (and analytical tools) aren't perfect, so there is a ton of trial and error to do to correctly.

How exactly do you edit a gene? Like, it is very, very small thing. How do you even measure it, let alone replace it?

xen2xen1 4y ago

Viruses do that an astounding number of times a day, every day, don't they? And this treatment uses a virus.

yCombLinks 4y ago
A virus that we've modified to deliver the genetic payload we want inserted at a specific point in this child's DNA. It's not "give this child a random virus we have laying around, that'll fix her".

yazaddaruvala 4y ago

Keywords to search for "CRISPR Cas9"

bglazer 4y ago

Biochemistry is wild! Measuring is an absolutely fascinating procedure. The predominant method is called sequencing by synthesis. Illumina is the company that basically rules the market for this technology, they have some decent explanatory videos if you’re interested. The first steps are to isolate DNA, then break it into small bits, replicate those small pieces thousands of times, and then anchor these to a glass slide. Then flow a solution over the slide with the individual DNA bases (ATCG) that have been modified to fluoresce when illuminated with a certain wavelength of light. These fluorescently labeled nucleotides get assembled one by one into strands that match the small fragments from the DNA sample. Each time the fluorescent DNA bases are added a laser is shined on the glass slide and a very sensitive microscope camera reads how many strands shone at the frequency that corresponds to A T C and G. This tells you which base just got added to which strand. Repeat a couple hundred times and you have a huge number of sequences of ATCG’s corresponding to each short strand of DNA in the sample. The problem now is assembling these short sequences into a full genome. Basically, the puzzle is finding the arrangement of short sequences that maximizes the overlap between them and their agreement with a reference genome. It’s a pretty interesting problem that (I believe) is classically solved with dynamic programming, although I don’t know the most recent methods. I really don’t think it’s well enough appreciated how integral computation is to DNA sequencing. Signal processing in the camera, assembling the genome fragments, determining whether a mutation exists, and all the subsequent analysis to give biological meaning to a sequence. Edit: editing is a whole other, extremely complicated procedure. In fact, direct editing isn’t really possible now. Instead we can basically just delete and insert.

aaauaucuggaa 4y ago
Your answer is much better
ruskyhacker 4y ago
Thank you for the detailed explanation!
syastrov 4y ago
It is super interesting! I was at a talk where a genetics company used the Smith-Waterman algorithm (1) to perform sequence alignment. Still I believe it took a long time (24 hours?) to perform the calculations. They were working on optimizing the code as doing so could mean a faster turnaround. 1. https://en.m.wikipedia.org/wiki/Smith–Waterman_algorithm https://en.m.wikipedia.org/wiki/Smith–Waterman_algorithm
wheelerof4te 4y ago
Thank you very much for the detailed explanation. This is the kind of content I visit this site for.

aaauaucuggaa 4y ago

With DNA sequencing?

l33t233372 4y ago
I believe the question could be more thoroughly phrased as “How does DNA sequencing work with such precision at such scales that we can edit DNA?” This formulation has the added benefit of not being easily answered with a flippant remark.

raffraffraff 4y ago

Vim or Emacs. But vim is better.

flir 4y ago
Yeah, if you want DNA littered with ESC, CTRL+c, CTRL+z, CMD+q, CMD+w, ALT+F4... Don't take the chance, people. Edit your DNA with notepad.
- raffraffraff 4y ago
  Noooo! Then you'll have ^M on each line!
ta1243 4y ago
Real molecular biologists use butterflys...

refurb 4y ago

Its similar to chemistry. You cant see molecules. We have a set of tools that let you determine biological structures (sometimes entirely, sometimes only partially). We also have a set of tools to modify genes. Some viruses already do this, so we use them. Were also using CRISPR which is based on the machinery of bacteria. So you use the modification tools to change genes and the analytical tools to prove you did it correctly. Of course the level of complexity is way higher since your dealing with a living organism and the modification tools (and analytical tools) aren't perfect, so there is a ton of trial and error to do to correctly.