Posts Tagged ‘genes’
Appeals Court Upholds Companies’ Right to Patent Genes, But the Future of Gene Research Remains Unclear
Two of the three judges are also scientists
The case involved patents on two human genes that are used to predict breast cancer, BRCA1 and BRCA2. To study these genes, patients and scientists will again have to pay a fee — up to $3,000 — to the company that owns the patent, Myriad Genetics.
In a 2-1 ruling, the Court of Appeals for the Federal Circuit, which specializes in patent law, overturned an earlier decision that invalidated the patents. The decision is still somewhat unclear, however, with three separate opinions and a half-dozen points of law under debate. The lack of clarity, and the complex and controversial nature of the case, makes a hearing by the high court seem likely.
The court did rule against Myriad in one aspect, involving the process they use to analyze a patient’s genes. This requires “abstract mental steps,” the court said. So the court said the genes themselves could be patented, but a specific method of studying them could not.
"We strongly support the Court's decision that isolated DNA and cDNA are patent-eligible material as both are new chemical matter with important utilities which can only exist as the product of human ingenuity," , president and CEO of Myriad Genetics. Scientists were not as pleased: "Genes or a sequence of the genome is a product of nature and should not be patentable," , president of the Association for Molecular Pathology, which brought the lawsuit.
The U.S. Trademark and Patent Office has already issued patents on more than 4,000 human genes, so a ruling that would invalidate gene patents would have major implications for the biotech industry. Companies like Myriad argue patents are necessary to protect product development and encourage innovation; opponents argue the ruling will stifle competitive research and jeopardize patient health, and that it’s unethical to patent something that comes from nature. The Obama administration had filed a brief arguing that isolated genes should not be patented.
Patents on plant and even animal genes have not risen to this level of controversy. and animals are big business for biotech firms, which license their gene patents to other companies that produce seeds, additives and other products. About is also patented, including genes associated with diseases like Alzheimer's. Other companies and researchers must pay fees to license the patent.
The court ruled that patents are allowed because once pieces of DNA are isolated from the body, their chemical structures differ from the DNA that exists inside the body — so they’re not actually products of nature. Two of the judges on the three-judge appellate panel are scientists, and brought their own analysis to the debate. Judge Alan D. Lourie, who as the holds a PhD in chemistry, concluded thusly:
In this case, the claimed isolated DNA molecules do not exist as in nature within a physical mixture to be purified. They have to be chemically cleaved from their chemical combination with other genetic materials. In other words, in nature, isolated DNAs are covalently bonded to such other materials. Thus, when cleaved, an isolated DNA molecule is not a purified form of a natural material, but a distinct chemical entity. In fact, some forms of isolated DNA require no purification at all, because DNAs can be chemically synthesized directly as isolated molecules.
Judge Kimberly A. Moore, who has a degree in electrical engineering, also discussed the chemical makeup of the isolated DNA, but also said the new sequences have a utility that whole gene sequences do not — in this case, predicting breast cancer risk.
Judge William C. Bryson, who does not list any scientific background on , was the sole dissenter, arguing that most people would argue patents are intended to protect inventions, and “a human gene is not an invention.”
Much legal wrangling remains to be done before this question is finally settled.
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Mice Engineered to Lack Muscle Contraction Gene Have Superior Endurance (and Humans Might, Too)
Mice that lack this gene, which is related to muscle contraction, can than their counterparts, a new study says — suggesting a genetic predisposition to endurance in some athletes.
Physiologists led by Tejvir Khurana at the University of Pennsylvania were studying IL-15Rα, which had been linked to proteins associated with muscle contraction. They engineered mice to lack that gene, and recorded the mice’s activity. Every night, the knockout mice ran six times farther than normal mice, according to the .
The team dissected the muscles in these marathon mice, and found the muscles had more fibers and more mitochondria, the power plants of cells, Science NOW reports. This meant the muscles took longer to tire and longer to use up their energy supplies. The researchers found that the lack of IL-15Rα coaxed one type of muscle cell to turn into another type — from fast-twitch, easily tired muscles into slower-contracting, longer-endurance muscles.
It turns out that endurance athletes also have IL-15Rα variations, which might help explain their stamina. Khurana et. al worked with some Australian researchers to study genetic samples from Olympians and other world-class athletes, and found certain genetic variants were more common in long-distance athletes than in sprinters, for instance.
The research is reported in the .
More work must be done to explain why the IL-15Rα knockout mice had such a proclivity for physical activity — no one coaxed them to run six times longer than their friends, they just did. So it’s not clear whether a lack of IL-15Rα made them hyperactive as well as tenacious. But “the work raises the possibility that drugs blocking IL-15Rα could one day enhance endurance,” Science NOW reports.
Until then, looks like I will just have to keep training.
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New Genome Editing Method Helps Scientists Rewrite Whole Sections of the Code of Life
Using a new genome engineering method, researchers from Harvard University and MIT were able to systematically replace one three-letter DNA “word,” or codon, with another one, throughout the entire genome. Their method reimagines genomes as editable templates, allowing entire sections to be rewritten without interrupting the overall organizational structure.
Ever since genome sequences were unraveled, scientists have been experimenting with ways to edit them, to give cells new capabilities and to cure diseases. But progress has been slow, in part because the editing job must be incredibly precise — one misplaced allele on a chromosome can be lethal. Introducing individual changes is therefore laborious and difficult.
Genetic scissors like zinc-finger nucleases can do the job, glomming on to certain sequences of a genome and cutting it out. Engineered viruses can then bring new DNA to the targeted area. Just last month, researchers successfully that cause hemophilia, in a study involving living mice.
Rather than using scissors, this new method is akin to the find-and-replace function on your word processor, seeking out individual codons and replacing all of them with something new. The researchers used E. coli bacteria and edited a codon that only appears 314 times in the genome, spelled TAG.
Most codons spell out the sequence of an amino acid, as a Harvard Medical School explains. But some codons direct a cell to stop adding amino acids to a protein chain. TAG is one such stop codon, and it happens to be the rarest word in the E. coli genome. The team used a method called multiplex automated genome engineering, or MAGE, to replace the TAG codon with another stop codon, TAA.
MAGE locates specific DNA sequences and replaces them with a new sequence as the cell copies its DNA. The team made 32 E. coli strains, each of which had 10 TAG codons replaced. Then they used a new technique called conjugative assembly genome engineering (CAGE), which allowed them to control the process that bacteria use to swap genetic material.
An evolutionary tournament of sorts reduced the number of strains to 16, each with double the amount of TAG edits that it started with; ultimately, a final four strains had one-fourth of all their TAGs replaced, .
The researchers believe they’re on track to replace all 314 of them — without harming the cells in any way.
The next step would be to take out the genetic sequences that allow the cell to read the TAG stop instructions. This machinery could then be used for an entirely new purpose, like encoding a new protein or function.
The research is described in today's issue of the journal Science.
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First Successful Use of Genome Editing In Living Animals Cures Hemophilia In Mice
Scientists say the research is a major step forward for gene therapy, which has long promised to cure disease by editing genetic sequences.
The therapy is based on enzymes called , which serve as a sort of genetic scissors. The enzymes are engineered to match a specific gene location on a chromosome, where they snip through DNA’s double helix.
In this case, researchers led by Katherine A. High, a hematologist and gene therapy expert at The Children’s Hospital of Philadelphia, used ZFN proteins that were engineered to snip through the location of a genetic mutation that causes hemophilia. Hemophiliacs lack a blood-clotting factor made by the liver that helps stanch bleeding, so their blood cannot clot, meaning minor injuries can be life-threatening.
High and colleagues had to take another step in their research, because hemophilic mice have a different genetic mutation than humans. They engineered mice to express the faulty human sequence, located on the F9 gene, and they designed ZFNs to cut through it. Then they engineered a virus that targets the liver (where the blood clotting factor is made) to carry the normal, unmutated version of F9.
As a result, the mutated section was removed, and the unmutated gene was inserted instead. Then the DNA molecule is stimulated to repair itself, sewing the new gene in place.
This is an improvement over other genetic editing techniques that use viruses to cut and paste the new genes. Although they have been shown to work, viral therapy has some inherent problems, including unpredictable chromosomal insertion, which can induce unwanted mutations. But the ZFN is designed to home in on a precise location of mutated DNA.
After this treatment, the animals’ blood clotted in 44 seconds, compared with more than a minute for hemophiliac mice, .
The study shows that zinc finger proteins and replacement genes can be used to induce changes in living animals, which is promising for a wide range of therapies. For instance, other researchers are using ZFNs to disrupt a gene that makes a receptor used by the AIDS virus, as the . People without that gene, CCR5, are naturally immune to HIV.
The mouse study is reported in this week's issue of the journal Nature.
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Has The “Gay Gene” Been Found in Female Mice?
Tweaking a single gene in female mice has been found to change their sexual preference
A group of Korean geneticists has altered the sexual preferences of female mice by removing a single gene linked to reproductive behavior. Without the gene, the mice gravitated toward mice of the same sex. Those mice who retained the gene, called FucM, were attracted to male mice. (FucM is short for fucose mutarotase.)
The geneticists' study, published last week in the journal explains that female mice without FucM avoided male mice, declined to sniff male urine, and made passes at other females.
Lead author Chankyu Park, of the Korea Advanced Institute of Science and Technology in South Korea, says this shows the absence of FucM tricks female mouse brains into functioning like male brains. "The mutant female mouse underwent a slightly altered developmental program in the brain to resemble the male brain in terms of sexual preference," he told the London .
Park said he now wants to research whether this finding has any relevance for humans.
The fact that he is in South Korea, where bioethics are notoriously may prove important as he goes forward. Research that gets anywhere close to searching for a gay gene -- even with animals -- has been highly controversial in the U.S., where cuts across the political spectrum. Some still remember a 1995 where scientists from the National Institutes of Health performed a similar procedure on male fruit flies, yielding what one journalist called "all-male conga lines." (For the record, the male flies became bisexual, not strictly gay.)
Even in South Korea, though, Park admits he may have trouble recruiting human volunteers for the next leg of his research.
Mara Hvistendahl is writing Unnatural Selection, a book on reproductive technology, sex selection, and gender imbalance.
New Genetic Model Accurately Predicts Who’s Likely to Live to 100
As part of the New England Centenarian Study, a team of aging research specialists led by Paola Sebastiani and Tom Perls looked at 300,000 genetic markers in 800 centenarians and compared their profiles with those of random individuals. They then developed a genetic model that can compute an individual's predisposition to living a long life and found that centenarians shared a common genetic signature that could predict extreme longevity -- with 77 percent accuracy. The findings represent a breakthrough in understanding how genes influence human life spans.
"Out of 100 centenarians we could correctly predict the outcome of 77 percent, while we incorrectly predicted the outcome of 23 percent," said Sebastiani. The researchers believe the 23 percent error rate can be attributed to genetic variance not yet known and included in the analysis, as well as other factors that influence longevity. "Making healthy lifestyle choices such as eating a well balanced diet or exercising regularly and avoiding exposure to tobacco plays an undisputed role in determining how each of us will age," said Andrew Sugden, international managing editor of Science.
Centenarians are a model of aging well, and 90 percent of people who reach this milestone are disability free at the average age of 93, Perls said. But he advised caution about the possibility of "testing" people to determine longevity, saying that much more study needs to be done regarding how health care providers and the research community guide individuals about what to do with the information they get. "I think a test for exceptional longevity is not quite ready for prime time," he said. "We're quite a ways from understanding what pathways governed by these genes are involved and how the integration of these genes, not just with themselves but with environmental factors, are all playing a role in this longevity puzzle."
According to Perls, future analysis of the results may shed light on how specific genes protect centenarians from common age-related diseases, such as dementia, heart disease, and cancer. "I look at the complexity of this puzzle and feel very strongly that this will not lead to treatments that will get a lot of people to become centenarians, but it could make a dent in the onset of age-related diseases like Alzheimer's," he said.
The results of the study were published today on the Science Express web site.
Study Turns Up Viral Key That Might Lead to Universal Flu Treatment
The influenza A virus contains eight individual single-stranded RNA segments, each of which has to make protein as well as new segments, in processes called transcription and replication. The multitasking strands must prioritize their work, so they must start with transcription and move on to replication. Researchers at Mount Sinai School of Medicine in New York figured out how to prevent RNA from starting the replication process. Their results were published June 1 online in the Proceedings of the National Academy of Sciences.
Using a novel process called deep sequencing, the team found a small viral RNA segment, or svRNA, that is integral to the change. Inhibiting the svRNA from doing its work stymies replication, and therefore slows the spread of the virus.
Even better, influenza A shares this trait with its viral cousins, influenza B and C, meaning the svRNA switch can be used to stop all kinds of flu -- even the H1N1 flu. As an added bonus, if the virus is prevented from replicating, it stays in transcription mode and produces more proteins. This helps the body's immune system build up its defenses, according to Benjamin tenOever, an assistant microbiology professor at Mount Sinai and a study author.
The process used to make this discovery is also groundbreaking, the researchers say. The deep sequencing allowed the scientists to obtain millions of small RNAs from cells in an unbiased fashion, according to a Mount Sinai release.
The next step is to find a way to introduce RNA "antagonists" to inhibit the svRNA's switch function, tenOever says. That's still a long way off, but the knowledge that RNA can be switched off means that a universal flu treatment is a possibility.
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