5 ms·

Certainly. That is with unaided, wild-type Cas9, 4 years ago. The understanding (and mitigation) of what causes those side-effects is under some of the most com

by jfarlow 10y ago

Certainly. That is with unaided, wild-type Cas9, 4 years ago. The understanding (and mitigation) of what causes those side-effects is under some of the most comprehensive and intense research as we speak. Searching PubMed for 'Cas9' shows that 2000 papers (of a total of 3200 results) have been written in the last 16 months. And there are other ways to edit genomes - Cas9 is great for research because it's fast, but there are likely less toxic ways to edit a live genome once you have used Cas9 in the lab to figure out what to actually edit. Further, the body is pretty resilient. You don't need viability to be 100% before a therapy could be successful. Chemotherapy kills a whole lot of cells and people survive it.

nonbel 10y ago
Is there a less toxic (but equally effective) cas9 available, or are you saying this is still under research? Sorry, I do not feel like searching around right now.
- jfarlow 10y ago
  Off the top of my head: Entirely new (smaller, thus more engineerable) Cas systems (1 month ago): http://www.nature.com/cr/journal/v27/n3/full/cr201721a.html http://www.nature.com/cr/journal/v27/n3/full/cr201721a.html Variously engineered Cas9 proteins to reduce toxicity the over wild-type protein (two months ago): https://www.ncbi.nlm.nih.gov/pubmed/28179977 https://www.ncbi.nlm.nih.gov/pubmed/28179977 Cas9-Inhibitors to help regulate activity (two months ago) http://www.cell.com/cell/fulltext/S0092-8674(16)31683-X http://www.cell.com/cell/fulltext/S0092-8674(16)31683-X And this doesn't include any ongoing research using other homing nuclease technologies like TALENs and Zn-Fingers that provide an entirely different set of tradeoffs but aren't as sexy, in part because they're harder to use.
  - nonbel 10y ago
    I didn't see any data on improved survival/toxicity in those papers. The closest was Fig S4B/C of the last one (Rauch et al 2017), which shows some of the inhibitors are toxic too. So evidence for that may exist somewhere, but not there. Also, I think if they were serious about addressing this toxicity issue they would be include simple charts of the number of cells over time and number of "modified" cells over time. Then they (and the reader) can easily compare the toxicity and efficacy of different techniques.

by jfarlow 10y ago

nonbel 10y ago

Is there a less toxic (but equally effective) cas9 available, or are you saying this is still under research? Sorry, I do not feel like searching around right now.

jfarlow 10y ago
Off the top of my head: Entirely new (smaller, thus more engineerable) Cas systems (1 month ago): http://www.nature.com/cr/journal/v27/n3/full/cr201721a.html http://www.nature.com/cr/journal/v27/n3/full/cr201721a.html Variously engineered Cas9 proteins to reduce toxicity the over wild-type protein (two months ago): https://www.ncbi.nlm.nih.gov/pubmed/28179977 https://www.ncbi.nlm.nih.gov/pubmed/28179977 Cas9-Inhibitors to help regulate activity (two months ago) http://www.cell.com/cell/fulltext/S0092-8674(16)31683-X http://www.cell.com/cell/fulltext/S0092-8674(16)31683-X And this doesn't include any ongoing research using other homing nuclease technologies like TALENs and Zn-Fingers that provide an entirely different set of tradeoffs but aren't as sexy, in part because they're harder to use.
- nonbel 10y ago
  I didn't see any data on improved survival/toxicity in those papers. The closest was Fig S4B/C of the last one (Rauch et al 2017), which shows some of the inhibitors are toxic too. So evidence for that may exist somewhere, but not there. Also, I think if they were serious about addressing this toxicity issue they would be include simple charts of the number of cells over time and number of "modified" cells over time. Then they (and the reader) can easily compare the toxicity and efficacy of different techniques.