Biologists who last year made a blockbuster — but controversial — claim that they had fixed a disease-causing mutation in human embryos using CRISPR gene editing have released fresh evidence in support of their work. Critics argued that the researchers’ evidence wasn’t persuasive and that the feat did not seem biologically plausible, intensifying the existing controversy surrounding the use of gene editing in human embryos to prevent diseases.
Now, a year after the study was published in Nature1, its authors, led by reproductive biologist Shoukhrat Mitalipov at the Oregon Health & Science University in Portland, have backed up their claims with new data2, published on 8 August alongside a pair of letters critiquing the original results.3,4.
Whatever happens next, it is likely that questions about whether it is possible to repair mutations in human embryos will persist until other researchers can repeat the feat — no easy task in a field that is strictly regulated, and even illegal in some countries.
Did CRISPR really fix a genetic mutation in these human embryos?
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One of the barriers to using CRISPR-Cas9 gene editing in the clinic is the possibility that the enzyme will clip DNA in the wrong spot. In a study published in Nature [DOI: 10.1038/s41586-018-0500-9] [DX] today (September 12), researchers describe a strategy to predict these off-target mutations throughout the genome and show in mice that a carefully designed guide RNA strand does not produce any detectable slip-ups.
The study confirms that "you'd better make sure that you've got a really accurate guide RNA," says Janet Rossant, a developmental biologist at the University of Toronto and the Hospital for Sick Children who did not participate in the work. "This [method] is a better way of testing for how specific that guide RNA will be before you go into animal models and, of course, into humans," she adds.
According to coauthor Marcello Maresca, a biologist at AstraZeneca in Sweden, one long-term goal of his company is to be able to use therapeutic gene editing to address a number of human diseases. "However, realizing the potential of CRISPR medicines requires the development of methods to enable the efficient modification of the target gene with no effects elsewhere in the genome," he writes in an email to The Scientist.
VIVO = "verification of in vivo off-targets".
Related: CRISPR Safer than Thought; Misleading Study Found Shared Mutations in Closely Related Mice
CRISPR Becomes More Precise
Paper That Found CRISPR "Off-Target Effects" Retracted
Repair of Double-Strand Breaks Induced by CRISPR Leads to Large Deletions and Complex Rearrangements
Did CRISPR Really Fix a Genetic Mutation in These Human Embryos?
(Score: 2) by MichaelDavidCrawford on Friday August 10 2018, @10:09AM
- First.
Genetic Counselors don't do DNA tests. They ask lots of odd questions such as what color hair the women in your family tend to have.
In the case of Lorenzo Odone, all the women in his mother's family had red hair. That and some other traits enabled a genetic counselor to diagnose Lorenzo's adrenoleukodystrophy.
That very rare genetic disease causes a buildup of a certain fatty acid in the blood. To much lipid in your blood and it will dissolve away the myelin sheaths that electrically insulate your nerves from your blood stream. That results in your pain receptors constantly firing.
It only struck young boys, and they always died by the age of twelve.
his parents Augusta and Michaela found an effective treatment by hanging out in a medical library for years on end: a highly-refined fatty acid.
If the human body doesn't get enough fatty acid Foo, then it will mistakenly produce fatty acid Bar. IIRC the buildup of Bar results from the body's inability to eliminate it. Or something like that. It's been a long time since I saw "Lorenzo's Oil".
That I took a date to such a tragic movie had me wanting to crawl under my seat but in the end she told me she got heavily into it.
At the very end they show a whole bunch of like boys saying "My name is $GIVEN_NAME and I take Lorenzo's Oil".
Yes I Have No Bananas. [gofundme.com]
(Score: 3, Interesting) by Anonymous Coward on Friday August 10 2018, @10:33AM (4 children)
Not fixing something like downs syndrome is morally equivalent to genetically engineering your child to have it.
(Score: 0) by Anonymous Coward on Friday August 10 2018, @11:01AM (1 child)
I doubt you could fix Down's with CRISPR since it is more than just a bad gene. Instead it's an entire chromosome that is duplicated (present as a triple).
(Score: 0) by Anonymous Coward on Friday August 10 2018, @11:24AM
Good point, but I didn't specifically intend to make a point about either down's or CRISPR. At present off target effects provide sufficient concern to make using CRISPR on cells which will become gametes a bad idea anyway. The intended point applies just as much to screening for the sake of abortion as genetic engineering. I was just triggered by being reminded that it's controversial to heal people in this way.
(Score: 0) by Anonymous Coward on Friday August 10 2018, @10:31PM (1 child)
Using your logic, we're a generation away from a negro-free Anerica?
(Score: 0) by Anonymous Coward on Saturday August 11 2018, @10:38PM
Allowing a baby to be born black is morally equivalent to ensuring it is born black.
I see no problem with ensuring a baby is a particular race, provided that it'll live in a society which treats that race well.
(Score: 0) by Anonymous Coward on Friday August 10 2018, @11:19AM (2 children)
The paper in question was reported here: https://soylentnews.org/article.pl?sid=17/08/03/0245212 [soylentnews.org]
And critique here: https://soylentnews.org/article.pl?sid=17/09/13/0124206 [soylentnews.org]
Also, here is what I said within an hour of seeing it:
This current work just shows they didnt detect any large deletions, which does go against the alternative explanation in the critique but not mine (which is by far the most simple explanation for these results).
The other thing they show is that there was some loss of heterogeneity (ie dad had a C at a certain site while mom had a T so embryo should have C/T, but they saw T/T) around the "edit" site which they attribute to the maternal sequence being used to replace the paternal one. This could mean something but they don't have any controls for some inexplicable reason. How often did this happen at sites not near the "edit" site, etc.
(Score: 0) by Anonymous Coward on Friday August 10 2018, @02:50PM (1 child)
I hope for their sakes that the donors of the sperm were dead. Unconditional child support liability being created in the lab here.
(Score: 0) by Anonymous Coward on Friday August 10 2018, @03:13PM
There was only one bonor:
(Score: 0) by Anonymous Coward on Friday August 10 2018, @08:09PM
Anticlimactic sonofabitch.