Can prime editing fix every harmful mutation in all our cells?

[FTM1000]

https://www.biorxiv.org/content/10.1101/2021.01.08.425835v1.full
Can prime editing fix every mutation in every type of cell in the body?. From what I read in the article the editing efficiency of prime editing using adeno-associated virus is 1.82%, so what prevent us from repeating the same treatment 100 times and reverse some mutation from a specific type of cell/tissue?. And what prevent us from doing it in other types of cells/tissues?.

I read about gene editing and try to understand the capabilities of current genome editing technologies like prime editing but since I don't have a significant knowledge in biology its quite hard to understand this just by reading articles.

 

[atyy]

For comparison, you may like to look at some gene therapy for spinal muscular atrophy that has been approved a few years ago.
https://www.healthline.com/health/spinal-muscular-atrophy/gene-therapy-for-spinal-muscular-atrophy
https://www.the-scientist.com/news-...y-and-cost-of-muscle-wasting-treatments-68144
https://www.statnews.com/2019/05/31/spinal-muscular-atrophy-zolgensma-price-critics/

There is also a therapy for acute lymphoblastic leukemia where the patient's blood cells are taken out, genetically modified, then put back into the patient's body.
https://www.fda.gov/news-events/pre...roval-brings-first-gene-therapy-united-states

 

[FTM1000]

For comparison, you may like to look at some gene therapy for spinal muscular atrophy that has been approved a few years ago.
https://www.healthline.com/health/spinal-muscular-atrophy/gene-therapy-for-spinal-muscular-atrophy
https://www.the-scientist.com/news-...y-and-cost-of-muscle-wasting-treatments-68144
https://www.statnews.com/2019/05/31/spinal-muscular-atrophy-zolgensma-price-critics/

There is also a therapy for acute lymphoblastic leukemia where the patient's blood cells are taken out, genetically modified, then put back into the patient's body.
https://www.fda.gov/news-events/pre...roval-brings-first-gene-therapy-united-states

So Zolgensma only works in 41 percent of the patients because it manage to change the DNA of cells in only small part of the neurons in the spine and brainstem?. If the treatment will repeat several times does it mean that the drug will replace the SMN gene in more neurons?.

 

[atyy]

So Zolgensma only works in 41 percent of the patients because it manage to change the DNA of cells in only small part of the neurons in the spine and brainstem?. If the treatment will repeat several times does it mean that the drug will replace the SMN gene in more neurons?.

The 41% is the percentage that met all 3 components of ability to thrive at 18 months of age. However, if one looks at other measures the percentages are higher (eg. 55% for ability to swallow thin liquids, 86% for freedom from non-oral feeding support, 95% for CHOP motor function scores greater than 40). But you are right that there is variability. I don't know if that is due to the number of cells that received additional DNA, or other factors. If it is the number of cells, I would guess the same as you that repeating several times will add DNA to more cells (but that is only a guess). Incidentally, the treatment doesn't replace the person's existing DNA, but adds DNA to the cell.

 

[FTM1000]

I would guess the same as you that repeating several times will add DNA to more cells (but that is only a guess).

so the same goes to prime editing and other genome editing methods?. what prevent prime editing or other genome editing method like CRISPR from fixing every harmful mutation in the body?.

 

[atyy]

so the same goes to prime editing and other genome editing methods?. what prevent prime editing or other genome editing method like CRISPR from fixing every harmful mutation in the body?.

It's hard to deliver the treatment to every cell, and even if it gets to every cell, the biochemical processes that do the editing may not occur in every cell (just because there are multiple steps involved and so many places for failures to occur).

 

[Ygggdrasil]

One issue with performing repeated rounds of gene editing is that the editors are delivered by a virus. Presumably, the body mounts an immune response against the virus such that subsequent applications of the virus will be less effective.

 

[FTM1000]

One issue with performing repeated rounds of gene editing is that the editors are delivered by a virus. Presumably, the body mounts an immune response against the virus such that subsequent applications of the virus will be less effective.

Is this the main reason for why gene editing treatments have a problem to "scale up" with repeated treatments?. There is a research about a way to overcome this problem?. There is a way to prevent the immune response to the particular virus?.