Saturday, December 21, 2013

The dawn of genetic engineering?

Some CRISPR links. This technology is for real. See earlier post CRISPR. Watch realtime action hereGeCKO knockout in human cells.

Zhang and Church raise $43M for new venture Editas.

Application to Cystic Fibrosis in human stem cells , Cataracts in mouse.
The Scientist: It was less than a year ago that scientists first applied CRISPR, a genome-editing technique, to human cells. In short order, the technique has taken off like wildfire. And now, two papers appearing in Cell Stem Cell today (December 5) show that CRISPR can be used to rewrite genetic defects to effectively cure diseases in mice and human stem cells.

“What’s significant about this is it’s taking CRISPR to that next step of what it can be used for, and in this case, it’s correcting mutations that cause disease,” said Charles Gersbach, a genomics researcher at Duke University, who was not involved in either study.

CRISPR stands for clustered regularly interspaced short palindromic repeats. These RNA sequences serve an immune function in archaea and bacteria, but in the last year or so, scientists have seized upon them to rewrite genes. The RNA sequence serves as a guide to target a DNA sequence in, say, a zygote or a stem cell. The guide sequence leads an enzyme, Cas9, to the DNA of interest. Cas9 can cut the double strand, nick it, or even knock down gene expression. After Cas9 injures the DNA, repair systems fix the sequence—or new sequences can be inserted.

In one of the new papers, a team from China used CRISPR/Cas9 to replace a single base pair mutation that causes cataracts in mice. The researchers, led by Jinsong Li at the Shanghai Institute for Biological Sciences, designed a guide RNA that led Cas9 to the mutant allele where it induced a cleavage of the DNA. Then using either the other wild-type allele or oligos given to the zygotes repair mechanisms corrected the sequence of the broken allele.

Li said that about 33 percent of the mutant zygotes that were injected with CRISPR/Cas9 grew up to be cataract-free mice. In an e-mail to The Scientist, Li said the efficiency of the technique was low, “and, for clinical purpose, the efficiency should reach 100 percent.”

Still, this was the first time CRISPR had been used to cure a disease in a whole animal, an advance that Jennifer Doudna, a leader in CRISPR technology at the University of California, Berkeley, said was encouraging. Both studies “show the potential for using the technology to correct disease-causing mutations, and that’s what very exciting here,” she said.

Hans Clevers, a stem cell researcher at the Hubrecht Institute in Utrecht, The Netherlands, led the other study, which used CRISPR/Cas9 to correct a defect associated with cystic fibrosis in human stem cells. The team’s target was the gene for an ion channel, cystic fibrosis transmembrane conductor receptor (CFTR). A deletion in CFTR causes the protein to misfold in cystic fibrosis patients.

Using cultured intestinal stem cells developed from cell samples from two children with cystic fibrosis, Clevers’s team was able to correct the defect using CRISPR along with a donor plasmid containing the reparative sequence to be inserted. The researchers then grew the cells into intestinal “organoids,” or miniature guts, and showed that they functioned normally. In this case, about half of clonal organoids underwent the proper genetic correction, Clevers said.

For both studies, the researchers did not have to make significant modifications to existing CRISPR protocols. Clevers said in an e-mail to The Scientist that, compared with other gene editing techniques, CRISPR was straightforward. “We tried TALENs [transcription activator-like effector nucleases] and Zinc finger approaches. CRISPR is exquisitely fast and simple,” Clevers said. Li agreed. “I think CRISPR/Cas9 system may be the easiest strategy to cure genetic disease than any other available gene-editing techniques,” he said.

One limitation of CRISPR is that the approach can create off-target effects—alterations to sites other than the target DNA. In both studies, off-target effects were relatively rare, said Gersbach. “While reducing off-target effects is a priority, it’s unrealistic to think you’d be able to get rid of all off-target effects,” he told The Scientist.

While the approach is far from ready for prime time, the results of both these studies show promise for future clinical potential. “I think each time an advance like this is made, people are more sure that this is a technique that is likely to be useful in treating humans,” said Doudna.


Butch said...

Let me first sterilise the comments section.

There are regular commenters on this blog who hae some wrong information. Ashkenazi jews do not have have the highest IQ's on earth...

The ethnic group that does has the highest income per household in america, their country of origin has a space programme, nuclear weapons and nuclear submarines. In the U.S, this ethnic group has the highest percentage of it's population to have a bachelors degree other than those from Taiwan. This ethnic group has a higher percentage of their population that has a bachelors degree(71.1% which is higher that Filipinos, Chinese Jews whites Hispanics and blacks. The reason this ethnic group does so well despite being from a third world country is the caste system in their country. Have you guessed it??? It's the Indians at the top of the caste system in india.
The indian american household average income is about $88500 a year which is higher that any other ethnic group in america. This is due to the selective immigration and the caste system

here is a complementary article on it. Courtesy of science.

ben_g said...

Steve what are your biggest safety and ethical concerns with regards to genetic engineering?

DK said...

Despite the recent advances, I continue to be skeptical of this technology's prospects for routine editing. It's sure to be a huge boon for simple experimental biology but it has to overcome a vary basic non-specificity barrier that I think is very difficult to do. Unless non-specific cleavage is below 10^/(-9) (something, I believe, that's unheard of with nucleases and perhaps in biology in general), per every successful edit, CRISPR-Cas9 will introduce at least several other mutations. In the cases where the fix is for a deadly affliction, the new mutations will mostly be benign - true. But the talk of genome-wide editing is nothing but wishful thinking at this point.

Rudel said...

"that's unheard of with nucleases"

That would be the masculine plural nominative of the second declension so therefore "nuclei."

BobSykes said...

"ase" indicates the molecule is an enzyme not an element.

Rudel said...

Then it is yet another scientific Latin neologism of the like that have been prevalent since the 17th century. A barbarism. Make up your own words and quit messing with the classics for no reason.

disqus_LUJWSJEndf said...

I hope with genetic editing we can avoid the inminent embryo genocide due to eugenics...

Rudel said...

It's already happening with the Chinese habit of aborting girls.

disqus_LUJWSJEndf said...

You could say it's already happening because the same leftists that are against eugenics also want killing babies to be a human right... for women only, and are already aborting left and right all over the world. But eugenics will make this even worse, almost like the holocaust, except this time it will be "right" because embryos don't have brains yet.

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