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Agribusiness isn’t interested in CRISPR for crops alone; livestock, too, will be widely gene edited in the near future.
The gene-spliced salmon contains an extra growth hormone gene, resulting in a fish that reaches market weight in half the time of a conventionally farmed salmon and without any changes to its nutritional content or any increased health risks for either the fish or the humans who eat it. Advocates
gases; Enviropig manure contained 75 percent less phosphorus, which could have been an enormous benefit to the planet and
What if, instead, scientists had somehow managed to edit the salmon’s genome to ramp up production of its own growth hormone gene without adding any foreign DNA? Would
Even some humans exhibit the equivalent of double muscling. In 2004, a team of physicians from Berlin published a remarkable study describing a boy who was extraordinarily muscular at birth, with bulging thigh and upper-arm muscles. The child continued to develop abnormally pronounced muscles through age four and could perform incredible feats of strength,
Another example of livestock gene editing comes from a Minnesota company called Recombinetics, which achieved the remarkable feat of genetically modifying cows to prevent them from growing horns. The company’s goal was to obviate the cruel but widespread practice of cattle dehorning, a common procedure in the U.S. and European dairy industries.
CRISPR will help bridge this gap by making disease modeling in other animals virtually as accessible as it has been in the mouse.
Gene editing is also being exploited to target genes implicated in neural disorders, taking advantage of the fact that monkey models are uniquely suited for the study of human behavioral and cognitive abnormalities. Although
Some scientists hope that pigs can offer even more: a vast, renewable source of whole organs for xenotransplantation into human recipients.
With easy-to-use gene editing, it surely won’t be long before consumers can order off-the-shelf enhancements to any dog breed.
Fully morphing the elephant genome into the woolly mammoth genome would involve changing over 1.5 million DNA letter differences between them, and there are no guarantees that edited elephant cells could be used to establish an actual pregnancy.
There is one way, at least, in which the power to edit the genes of other species could prove to be more dangerous than any changes humans have made to the planet so far. 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.
Enter CRISPR. 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. In essence, the idea relies on a gene knock-in approach, in which scientists use CRISPR to cut DNA at an exact location and insert a new sequence of letters into the breach. There is one major difference with a gene drive, however: part of the new DNA added in contains the genetic information that encodes CRISPR itself.
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. Within half
insects. CRISPR gene drives, by contrast, are self-sustaining; since the mode of inheritance appears to outsmart natural selection, the modified insects
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.
amok. One of these is the so-called reversal drive, a gene drive that essentially functions as an antidote by overwriting any changes in the genome created by the original gene drive.
There’s also no way to guarantee that this incredibly powerful tool won’t wind up in the hands of people who have no compunction about using gene drives to cause harm—and who may, indeed, be attracted to them for exactly that purpose. 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.
was electrified by this news, although I can’t say that I was surprised, given how rapidly the technology was being implemented. Still, the researchers’ accomplishment represented something momentous: 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.
Germ cells are any cells whose genome can be inherited by subsequent generations, and thus they make up the germline of the organism—the stream of genetic material that is passed from one generation to the next.
Somatic cells are virtually all the other cells in an organism: heart, muscle, brain, skin, liver—any cell whose DNA cannot be transmitted to offspring.
power. 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.
Ethically speaking, editing somatic cells to treat genetic disease is much more straightforward than editing germ cells, since the changes can’t be passed down to the patient’s descendants.
Practically, however, it’s much more complex. Reversing a disease-causing mutation in a single human germ cell is much simpler than trying to do the same thing inside some of the fifty trillion somatic cells that make up a human body. To
Since the effects of genetic diseases tend to be localized in this way, therapies will need to treat cells in the most affected parts of the body.
That’s not to say it’ll be easy to get CRISPR to these locations, much less get it inside the cells themselves. This delivery problem is one of the greatest challenges that somatic gene-editing technologies will have to face.
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.
Because ex vivo gene editing requires doctors to first remove diseased cells from the body, it is uniquely suited to treating blood-based diseases.
doing so are simply too invasive and too risky. To treat these diseases, we’ll need to deliver CRISPR into the patient’s body, to the tissue where the disease is exerting its greatest effect.
Physicians must figure out how to get CRISPR into the tissues that are most affected by a given disease. In addition, this must be accomplished without provoking an immune response in the patients’ bodies. Furthermore, Cas9 and its RNA guide will have to be stable enough to survive inside the body until editing is completed.
To address these challenges, some CRISPR researchers are turning to one of their favorite delivery vehicles: viruses.
carrier of genetic information—has been an especially big asset to researchers developing in vivo gene-editing therapies: an innocuous human virus known as adeno-associated virus (AAV). AAV provokes only a mild immune response and is not known to cause any human disease.
encouraging aspect of AAV is its sheer natural diversity. By isolating different strains of the virus and then mixing and matching them in different ways, researchers have assembled a family of AAV vectors that can target cells in many different types of tissues.
chromosome and males possess only one X chromosome (paired with a paternally inherited Y chromosome), a single mutated copy of DMD leaves them wholly devoid of healthy dystrophin.
Females, however, have two X chromosomes and thus two copies of DMD; as long as one of the two copies is healthy, it can stave off the disease’s awful symptoms. While these females are spared, however, they remain carriers of the disease and will transmit the mutated DMD gene to roughly half of their male offspring. (This inheritance pattern makes DMD an example of an X-linked recessive genetic disease.)
that the ravages of the disease could be reversed. By packaging genetic instructions for CRISPR into AAV vectors, the researchers repaired skeletal and cardiac muscle cells, either by injecting the loaded viruses into the mouse’s muscles or by delivering the viruses to the same tissues through the bloodstream. They succeeded in turning on the healthy dystrophin genes, and the treated mice even showed substantial enhancement in muscle
the viral world alone, there’s a menagerie of retooled viral Trojan horses available for use, each with its unique set of advantages and disadvantages.
One example is the adenovirus, which causes the common cold among other illnesses (and assists adeno-associated viruses during infections, giving AAV their name). After gutting these adenoviruses and removing their pathogenic genes,
And then there are in vivo delivery strategies that won’t use viruses at all. Building on advances in nanotechnology—the science of fabricating submicroscopic structures—researchers are exploring the use of lipid nanoparticles to ferry CRISPR throughout the body. Resistant to degradation and easy to manufacture, these delivery vehicles also have the benefit of releasing the Cas9 protein and its guide RNA into the patient’s body in a regimented way.
lipid nanoparticles deliver CRISPR so that it acts quickly before being broken down by the natural recycling factories of the cell.
causing mutations was rather limited: scientists could detect and diagnose mutations in biopsies taken from patients, and they could study a small number of discrete mutations in mouse models.
The ability to target many genes at once is one of CRISPR’s greatest attributes. Unlike the gene-editing technologies that preceded CRISPR, the process
Sabatini’s team wanted to discover gene mutations that disabled the cancer. In other words, they wondered whether there were genes that the cancerous cells absolutely depended on for their pathogenicity and couldn’t live without. In
A revolutionary form of cancer treatment, immunotherapy is a departure from the three main types—surgery, radiation, and chemotherapy—that doctors have historically employed. Unlike these older approaches, cancer immunotherapy aims to use a patient’s own immune system to hunt down and destroy dangerous cells. In a complete paradigm shift, immunotherapy targets not the cancer, but the patient’s own body, empowering it to fight cancer on its own.
It seems likely that gene editing will go a step further and transform cancer immunotherapy into more of an off-the-shelf treatment, where a single batch of engineered T cells, designed for a specific type of cancer, could be given universally to all patients suffering from that pathology.
immunocompatible). Finally, the T cells contained edits to another gene that gave them a kind of invisibility cloak so that they could survive longer in Layla’s body.
Usually, some degree of off-target activity is unavoidable, which is why every drug on the market carries warnings of side effects—but when it comes to gene editing, side effects could be especially dangerous. After all, the side effects of a medication typically cease once a patient stops taking the drug. With gene editing, however, any off-target DNA sequence, once edited, is irreversibly changed. Not only will unintended edits to the DNA be permanent, they will also be copied into every cell that descends from the first one.
that even a single mutation can be enough to wreak havoc on an organism.
Luckily, off-target edits made by CRISPR, like other gene-editing technologies, tend to be fairly predictable, since they affect only the DNA sequences that are most similar to the matching guide RNA. If CRISPR is programmed to target a twenty-letter sequence in gene X, but gene Y has a similar DNA sequence that differs in only one letter, there is a finite probability that CRISPR will introduce edits in both genes. The less closely the two sequences mirror each other, the lower the likelihood of off-target mutations.
Multiple laboratories have written computer algorithms that will automatically probe the three-billion-letter human genome to see how many other regions have sequences similar to the one a scientist wants to edit. If
