5 ms·

Super-precise CRISPR tool enters US clinical trials for first time

30 points by Vagantem 3y ago

heyoni 3y ago
If I’m understanding this correctly, this procedure is performing a single strand cut rather than double strand? Are there any base editing systems that can perform point edits without the cells repair mechanisms?
- dillydogg 3y ago
  I think it depends what you mean by point edits, but essentially no, we always take advantage of the host DNA repair mechanisms. Base editing technology (which were also used in the primary studies) direct enzymes to DNA bases that result in unnatural DNA bases that are repaired into natural ones. These are very effective when you want to make a single base pair mutation. There are systems that include a reverse transcriptase that allow you to edit bases more directly, but these also rely on cell DNA repair mechanisms.
  - heyoni 3y ago
    I'm thinking about genetic diseases occurring in non-dividing cells like cortical neurons as a possibility. It seems like as long as the technology relies on NHEJ or HDR this kind of editing won't be possible as a therapy.
    - dillydogg 3y ago
      NHEJ works in non-dividing cells, though HR requires it. Many of these techniques (prime editing in particular) use exogenous enzymes to mediate some of the repair and can work in non-dividing cells.
      - heyoni 3y ago
        I must have misread some literature so thanks for clearing that up. I'm now seeing that it only requires a homologous template which, hypothetically could even be provided by the therapeutic agent itself?
        dillydogg 3y ago
        Yes, this is actually how prime editing works! You also attach some reverse transcriptase to perform the base insertion (but the repair requires cellular help, prime editing works in non-dividing cells though!)
        heyoni 3y ago
        Is prime editing possible for diseases that result from point mutations? I know tat there’s always the issue of getting the construct into the cells and then into the nucleus but can we confidently elicit base edits in humans? All I’ve seen (and I haven’t seen everything) is crispr mediated transcription in Duchene muscle dystrophy but it failed. I’m looking at possible cures for satb2 but was under the impression that NHEJ wasn’t viable for some reason (my notes suck).

30 points by Vagantem 3y ago

If I’m understanding this correctly, this procedure is performing a single strand cut rather than double strand? Are there any base editing systems that can perform point edits without the cells repair mechanisms?

dillydogg 3y ago
I think it depends what you mean by point edits, but essentially no, we always take advantage of the host DNA repair mechanisms. Base editing technology (which were also used in the primary studies) direct enzymes to DNA bases that result in unnatural DNA bases that are repaired into natural ones. These are very effective when you want to make a single base pair mutation. There are systems that include a reverse transcriptase that allow you to edit bases more directly, but these also rely on cell DNA repair mechanisms.
- heyoni 3y ago
  I'm thinking about genetic diseases occurring in non-dividing cells like cortical neurons as a possibility. It seems like as long as the technology relies on NHEJ or HDR this kind of editing won't be possible as a therapy.
  - dillydogg 3y ago
    NHEJ works in non-dividing cells, though HR requires it. Many of these techniques (prime editing in particular) use exogenous enzymes to mediate some of the repair and can work in non-dividing cells.
    - heyoni 3y ago
      I must have misread some literature so thanks for clearing that up. I'm now seeing that it only requires a homologous template which, hypothetically could even be provided by the therapeutic agent itself?
      - dillydogg 3y ago
        Yes, this is actually how prime editing works! You also attach some reverse transcriptase to perform the base insertion (but the repair requires cellular help, prime editing works in non-dividing cells though!)
        heyoni 3y ago
        Is prime editing possible for diseases that result from point mutations? I know tat there’s always the issue of getting the construct into the cells and then into the nucleus but can we confidently elicit base edits in humans? All I’ve seen (and I haven’t seen everything) is crispr mediated transcription in Duchene muscle dystrophy but it failed. I’m looking at possible cures for satb2 but was under the impression that NHEJ wasn’t viable for some reason (my notes suck).