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Researchers at UC Berkeley used CRISPR to generate a bizarre array of bodily transformations in crustaceans—gills growing where they shouldn’t be, claws becoming legs, jaws turning into antennae, and swimming limbs becoming walking limbs.
strategy is being undertaken in Europe to bring back the auroch, a wild ox that went extinct in the early 1600s,
in the Galápagos Islands to resurrect a species of saddleback tortoise from Pinta Island whose last known member died in 2012.
instance, the Pyrenean ibex, a wild goat, died out in 1999, but cryogenic preservation of skin biopsies taken from the last living specimen allowed Spanish scientists to implant its genetic material into the egg of a domestic goat. (The same procedure was used to clone Dolly the sheep in 1996.)
With the live birth that resulted, the scientists achieved the first-ever resurrection of an extinct animal, though, regrettably, the newborn died just minutes after birth.
The same cloning approach is now being pursued by Russian and South Korean scientists who are hoping to use mammoth tissues recovered in eastern Russia to resurrect woolly mammoths. CRISPR offers another way to bring bygone species back to life—one not so different from the fictional depiction of dino...
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similar strategy is being pursued for woolly mammoths by a team of Harvard researchers led by George Church.
Long Now Foundation, thinks so; its mission is to “enhance biodiversity through the genetic rescue of endangered and extinct species” using the tools of genetic engineering and conservation biology,
Compared to what we’ve done to our planet already, whether intentional or not, is CRISPR-based gene editing any less natural or any more harmful?
I’m referring to a revolutionary technology known as a gene drive, so called because it gives bioengineers a way to “drive” new genes—along with their associated traits—into wild populations at unprecedented speeds, a kind of unstoppable, cascading chain reaction.
Just a year after it was first proposed in a theory paper, CRISPR gene drives proved effective, first in fruit flies and then in mosquitoes.
there are certain DNA sequences, called selfish genes, that can increase their frequency in the genome with each generation, even without conferring any fitness advantage on the offspring.
In the summer of 2014, George Church’s team at Harvard, led by Kevin Esvelt, proposed a way to design and build gene drives with the help of efficient gene editing.
CRISPR gene drive can autonomously copy itself into new chromosomes, allowing it to grow exponentially within a population.
By combining CRISPR with various genetic payloads, such as pathogen-resistance genes, Esvelt theorized, scientists could program CRISPR to copy not only itself, but any other desirable DNA sequences.
early 2015, Ethan Bier and his student Valentino Gantz at UC San Diego reported the first successful demonstration of a CRISPR gene drive in the common fruit fly, using it to drive a defective pigmentation gene into the genome.
The result: 97 percent of the edited flies were a new, light yellow color instead of the species’ usual yellow-brown.
British team of researchers—among them Austin Burt, the biologist who pioneered the gene drive concept—created highly transmissive CRISPR gene drives that spread genes for female sterility.
Since the sterility trait was recessive, the genes would rapidly spread through the population, increasing in frequency until enough females acquired two copies, at which point the population would suddenly crash.
If sustained in wild-mosquito populations, it could eventually lead to outright extermination of an entire mosquito species.
Using CRISPR to build gene-drive mosquitoes
Another approach being developed by a British company called Oxitec involves inserting a lethal gene into the mosquito genome, and field trials have already commenced in Malaysia, Brazil, and Panama. However, these strategies are inherently self-limiting; the genetic alterations are rapidly eliminated by natural selection, and the only way to make a dent in mosquito populations is to repeatedly release large batches of the modified insects. CRISPR gene drives, by contrast, are self-sustaining; since the mode of inheritance appears to outsmart natural selection, the modified insects propagate
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This thoroughness is what makes gene drives so powerful—and so alarming. It’s been estimated that, had a fruit fly escaped the San Diego lab during the first gene drive experiments, it would have spread genes encoding CRISPR, along with the yellow-body trait, to between 20 and 50 percent of all fruit flies worldwide.
The ETC Group, a biotech watchdog organization, worries that gene drives—what they call “gene bombs”—could be militarized and weaponized to target the human microbiome or major food sources.
As Austin Burt wrote, “Clearly, the technology described here is not to be used lightly. Given the suffering caused by some species, neither is it obviously one to be ignored.”
Among the applications that have been proposed are reversing the genetic causes of herbicide and pesticide resistance that have evolved among organisms that threaten agriculture; promoting biodiversity by controlling, even eradicating, invasive species populations like Asian carp, cane toads, and mice; and stamping out infectious diseases such as Lyme disease, which is caused by certain bacteria transmitted by ticks, and schistosomiasis, caused by flatworm parasites transmitted by aquatic snails. But the most momentum, by far, is in the push to use gene drives to target the mosquito.
The mosquito causes more human suffering than any other creature on earth. Mosquito-borne diseases—malaria, dengue virus, West Nile virus, yellow fever virus, Chikungunya virus, Zika virus, and many others—have an annual death toll in excess of one million.
the allure of solving biological problems with biology.
Would it be a blessing or a curse to suddenly be rid of the winged pests that have inhabited the earth for more than one hundred million years?
Still, like many scientists, I sometimes can’t help but view the work being done with plants and animals as a sort of dry run for the ultimate goal of gene editing. I’m referring, of course, to the idea that Emmanuelle and I had when we first contemplated the outcome of our research collaboration: the dream that, someday, our work would help rewrite the DNA in human patients to cure disease.
in the Bay Area, I had the privilege of launching the Innovative Genomics Institute, aimed at harnessing technologies like CRISPR to lead the revolution in genetic engineering and fight against disease.
team of Chinese researchers programmed the same CRISPR molecules to find and fix a single-letter mutation among the 2.8 billion DNA letters of the mouse genome. In so doing, they performed the first outright, CRISPR-based cure of a genetic disease in a live animal.
It was the first of a new breed of exquisitely precise genetic therapies and seemed to mark the beginning of a new era in medicine—one in which at least some of the more than seven thousand human genetic diseases caused by a defined, single-gene mutation might be cured, thanks to a one-size-fits-all molecular tool.
experiments from China had cured a mouse of congenital cataracts,
Over the next couple of years, scientists used CRISPR to cure live mice of muscular dystrophy (a severe muscle-wasting disease), as well as various...
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Whether the underlying problem was incorrect letters of DNA, missing letters, extraneous letters, or even large chromosomal abnormalities, it seemed that no single-gene error was too great for CRISPR to fix.
Deciding what types of cells to target is one of the many dilemmas confronting researchers—should they edit somatic cells (from the Greek soma, for “body”) or germ cells (from the Latin germen, for “bud” or “sprout”)?
Normally, by the time a mouse with a disease-causing genetic mutation reaches adulthood, it’s too late to correct the error; what began as a mistake in a single fertilized egg cell has been copied into billions of descendant cells, making it all but impossible to stamp out every last trace of the disease.
focusing on the germline, scientists can send CRISPR into the embryo at its earliest stage of development and reverse the mutation in a single cell.
As the embryo develops into an adult organism, the repaired DNA is faithfully copied into every daughter cell, including the germ cells that will eventually transmit the genome to subsequent generations.
The distinction between somat...
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The available delivery strategies can be broken down into two major categories: in vivo gene editing (from the Latin for “within the living,” as mentioned earlier) and ex vivo gene editing (from the Latin for “out of the living”). In the former approach, CRISPR is sent directly into the body of the patient to do its work onsite; in the latter, the patient’s cells are edited outside of the body and then placed back into the patient.
the general intervention strategy is the same: remove the patient’s cells, correct them in a test tube, then put them back into the patient.
Believe it or not, some lucky people are naturally resistant to HIV. These individuals lack thirty-two letters of DNA in the gene for a protein called CCR5, which is located on the surface of white blood cells—those
This specific, thirty-two-letter deletion causes the CCR5 protein to be truncated and prevents it from making its way to the cell surface.
Without CCR5 proteins to attach to, HIV molecules can’t infect the cells.
10 to 20 percent of Caucasians possess one copy of the mutated gene, and homozygous individuals—those who possess two copies—are completely resistant to HIV. Roughly 1 to 2 percent of Caucasians worldwide (most of them in northeastern Europe) are fortunate enough to have this trait.
One approach involves programming CRISPR to target genetic material from the HIV virus, ridding patients’ cells of HIV by literally snipping the infectious DNA out of their genomes.
Yet another method might be best described as “shock and kill”: it uses a deactivated form of CRISPR to intentionally awaken the dormant virus so that it can be targeted using existing drugs.
Furthermore, Cas9 and its RNA guide will have to be stable enough to survive inside the body until editing is completed. In vivo CRISPR therapy
