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posted by martyb on Tuesday June 12 2018, @03:26AM   Printer-friendly
from the debugging-the-debugging-of-wetware dept.

Editing cells' genomes with CRISPR-Cas9 might increase the risk that the altered cells, intended to treat disease, will trigger cancer, two studies published on Monday warn — a potential game-changer for the companies developing CRISPR-based therapies.

[...] The CEO of CRISPR Therapeutics, Sam Kulkarni, told STAT the results are "plausible." Although they likely apply to only one of the ways that CRISPR edits genomes (replacing disease-causing DNA with healthy versions) and not the other (just excising DNA), he said, "it's something we need to pay attention to, especially as CRISPR expands to more diseases. We need to do the work and make sure edited cells returned to patients don't become cancerous."

Another leading CRISPR scientist, who asked not to be named because of involvement with genome-editing companies, called the new data "pretty striking," and raised concerns that a potential fatal flaw in some uses of CRISPR had "been missed."

[...] "We found that cutting the genome with CRISPR-Cas9 induced the activation of ... p53[*]," said Emma Haapaniemi, the lead author of the Karolinska study. That "makes editing much more difficult."

The flip side of p53 repairing CRISPR edits, or killing cells that accept the edits, is that cells that survive with the edits do so precisely because they have a dysfunctional p53 and therefore lack this fix-it-or-kill-it mechanism.

I've been skeptical about this for awhile, and arguing this exact point: double stranded breaks would induce the majority of cells with the target sequence to self-destruct, lyse, or go senescent. I've seen this reflected in the data on cell counts of almost every paper that includes it. Things are much worse than I thought if "leading CRISPR scientists" are now acting surprised at this.

[*] Entry on Wikipedia for p53 states:

Tumor protein p53, also known as p53, cellular tumor antigen p53 (UniProt name), phosphoprotein p53, tumor suppressor p53, antigen NY-CO-13, or transformation-related protein 53 (TRP53), is any isoform of a protein encoded by homologous genes in various organisms, such as TP53 (humans) and Trp53 (mice). This homolog (originally thought to be, and often spoken of as, a single protein) is crucial in multicellular organisms, where it prevents cancer formation, thus, functions as a tumor suppressor.[5] As such, p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation.[6] Hence TP53 is classified as a tumor suppressor gene.[7][8][9][10][11] (Italics are used to denote the TP53 gene name and distinguish it from the protein it encodes.)

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  • (Score: 0) by Anonymous Coward on Tuesday June 12 2018, @04:07AM (3 children)

    by Anonymous Coward on Tuesday June 12 2018, @04:07AM (#691771) make an alteration in the evolvement of an organic life system is fatal. A coding sequence cannot be revised once it's been established.

    • (Score: 2) by Immerman on Tuesday June 12 2018, @04:51AM (1 child)

      by Immerman (3985) on Tuesday June 12 2018, @04:51AM (#691780)

      Life is fatal - nobody has ever gotten out of it alive.

      The real question is, what is the cost/benefit ratio of any activity that shortens expected life?

      You could easily extend your expected lifespan by 10-30% (I forget exactly) by being castrated before puberty - yet most people obviously consider that benefit to not be worth the cost.

      • (Score: 0) by Anonymous Coward on Tuesday June 12 2018, @08:51AM

        by Anonymous Coward on Tuesday June 12 2018, @08:51AM (#691837)

        Life is fetal, you insensitive clod!

    • (Score: 2) by darkfeline on Tuesday June 12 2018, @07:03PM

      by darkfeline (1030) on Tuesday June 12 2018, @07:03PM (#692055) Homepage

      Clearly you have never used Emacs. Not only is it possible to rewrite parts of an Emacs process live, you can even hook into it with a debugger, again while the process is running. Heck, you can even hook into the debugger with the debugger and modify the debugger (either one) at the same time.

      Join the SDF Public Access UNIX System today!
  • (Score: 1, Insightful) by Anonymous Coward on Tuesday June 12 2018, @07:41AM (1 child)

    by Anonymous Coward on Tuesday June 12 2018, @07:41AM (#691817)

    Things are much worse than I thought if "leading CRISPR scientists" are now acting surprised at this.

    Of course they're acting surprised. If they don't they might get in trouble for fraud.

    • (Score: 5, Interesting) by Immerman on Tuesday June 12 2018, @02:03PM

      by Immerman (3985) on Tuesday June 12 2018, @02:03PM (#691897)

      I suspect it's more a matter of application-specific myopia. CRISPR has thus far been primarily used for creating GMOs. Modify 10,000 zygotes, and then breed your organism from the healthy survivors. No problem. Runaway tumors, etc. just exclude those individuals from the "healthy survivors" group.

      Therapeutic uses care far more about the long term consequences on *all* the cells modified - something alien enough to the common usage that I'm not at all surprised researchers didn't consider it when wrapped up in the excitement of the potential.

      Heck - in a similar vein I recall a TED talk by a neurological researcher who had modified a virus to cause specific kinds of neurons to grow different light receptors on their membranes, allowing them to be precisely fired or suppressed by fiber optic implants. He made a big deal about how he used a completely innocuous virus that didn't even cause a runny nose in most people, and the only thing I could think was "No, it WAS completely innocuous, but now you've released a contagious, almost symptom-free virus into the world that causes people's neurons to grow photoreceptors, with unknown long-term consequences." I have to admit when the zika "mild virus that causes microencephaly" thing exploded I felt compelled to look up whether it was the same kind of virus (it wasn't).