PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Editing the genome with high precision

New method allows scientists to insert multiple genes in specific locations, delete defective genes

2013-01-04
(Press-News.org) CAMBRIDGE, MA -- Researchers at MIT, the Broad Institute and Rockefeller University have developed a new technique for precisely altering the genomes of living cells by adding or deleting genes. The researchers say the technology could offer an easy-to-use, less-expensive way to engineer organisms that produce biofuels; to design animal models to study human disease; and to develop new therapies, among other potential applications.

To create their new genome-editing technique, the researchers modified a set of bacterial proteins that normally defend against viral invaders. Using this system, scientists can alter several genome sites simultaneously and can achieve much greater control over where new genes are inserted, says Feng Zhang, an assistant professor of brain and cognitive sciences at MIT and leader of the research team.

"Anything that requires engineering of an organism to put in new genes or to modify what's in the genome will be able to benefit from this," says Zhang, who is a core member of the Broad Institute and MIT's McGovern Institute for Brain Research.

Zhang and his colleagues describe the new technique in the Jan. 3 online edition of Science. Lead authors of the paper are graduate students Le Cong and Ann Ran.

Early efforts

The first genetically altered mice were created in the 1970s by adding small pieces of DNA to mouse embryonic cells. This method is now widely used to create transgenic mice for the study of human disease, but, because it inserts DNA randomly in the genome, researchers can't target the newly delivered genes to replace existing ones.

In recent years, scientists have sought more precise ways to edit the genome. One such method, known as homologous recombination, involves delivering a piece of DNA that includes the gene of interest flanked by sequences that match the genome region where the gene is to be inserted. However, this technique's success rate is very low because the natural recombination process is rare in normal cells.

More recently, biologists discovered that they could improve the efficiency of this process by adding enzymes called nucleases, which can cut DNA. Zinc fingers are commonly used to deliver the nuclease to a specific location, but zinc finger arrays can't target every possible sequence of DNA, limiting their usefulness. Furthermore, assembling the proteins is a labor-intensive and expensive process.

Complexes known as transcription activator-like effector nucleases (TALENs) can also cut the genome in specific locations, but these complexes can also be expensive and difficult to assemble.

Precise targeting

The new system is much more user-friendly, Zhang says. Making use of naturally occurring bacterial protein-RNA systems that recognize and snip viral DNA, the researchers can create DNA-editing complexes that include a nuclease called Cas9 bound to short RNA sequences. These sequences are designed to target specific locations in the genome; when they encounter a match, Cas9 cuts the DNA.

This approach can be used either to disrupt the function of a gene or to replace it with a new one. To replace the gene, the researchers must also add a DNA template for the new gene, which would be copied into the genome after the DNA is cut.

Each of the RNA segments can target a different sequence. "That's the beauty of this — you can easily program a nuclease to target one or more positions in the genome," Zhang says.

The method is also very precise — if there is a single base-pair difference between the RNA targeting sequence and the genome sequence, Cas9 is not activated. This is not the case for zinc fingers or TALEN. The new system also appears to be more efficient than TALEN, and much less expensive.

The research team has deposited the necessary genetic components with a nonprofit called Addgene, making the components widely available to other researchers who want to use the system. The researchers have also created a website with tips and tools for using this new technique.

Engineering new therapies

Among other possible applications, this system could be used to design new therapies for diseases such as Huntington's disease, which appears to be caused by a single abnormal gene. Clinical trials that use zinc finger nucleases to cut out the gene and replace it with the normal version are now under way, and the new technology could offer a more efficient alternative.

The system might also be useful for treating HIV by removing patients' lymphocytes and mutating the CCR5 receptor, through which the virus enters cells. After being put back in the patient, such cells would resist infection.

This approach could also make it easier to study human disease by inducing specific mutations in human stem cells. "Using this genome editing system, you can very systematically put in individual mutations and differentiate the stem cells into neurons or cardiomyocytes and see how the mutations alter the biology of the cells," Zhang says.

In the Science study, the researchers tested the system in cells grown in the lab, but they plan to apply the new technology to study brain function and diseases.

### The research was funded by the National Institute of Mental Health; the W.M. Keck Foundation; the McKnight Foundation; the Bill & Melinda Gates Foundation; the Damon Runyon Cancer Research Foundation; the Searle Scholars Program; and philanthropic support from MIT alumni Mike Boylan and Bob Metcalfe, as well as the newscaster Jane Pauley.

Written by Anne Trafton, MIT News Office END


ELSE PRESS RELEASES FROM THIS DATE:

An embryo that is neither male nor female

2013-01-04
So, is it a girl or a boy? This is the first question parents ask at the birth of an infant. Though the answer is obvious, the mechanism of sex determination is much less so. Researchers at the University of Geneva (UNIGE) attempt to shed light on this complex process by identifying the crucial role played by insulin and IGF1 and IGF2 growth factors, a family of hormones known for its role in metabolism and growth. In the absence of these factors at the time of sex determination, embryos do not differentiate into either male or female and have no adrenal glands. The results ...

Turning smartphones into secure and versatile keys

Turning smartphones into secure and versatile keys
2013-01-04
Smartphones and tablets have become an integral part of our daily lives. The capabilities of these handily sized mini-computers seem almost boundless as we phone friends, shoot holiday snaps, lose ourselves in a new music download or access the internet to obtain the boarding card for our next fl ight in comfort. Does it not seem logical, then, that we should make use of these constant companions as the key to our cars, front doors or lockers as well? A few such solutions are already available, but what's still missing is widespread market acceptance. At this year's CeBIT ...

Scientists discover how deadly skin cancer spreads into other parts of the body

Scientists discover how deadly skin cancer spreads into other parts of the body
2013-01-04
After recently announcing success in eliminating melanoma metastasis in laboratory experiments, scientists at Virginia Commonwealth University Massey Cancer Center have made another important discovery in understanding the process by which the gene mda-9/syntenin contributes to metastasis in melanoma (the spread of skin cancer) and possibly a variety of other cancers. Published in the journal Cancer Research, the study demonstrated that mda-9/syntenin is a key regulator of angiogenesis, the process responsible for the formation of new blood vessels in tumors. Mda-9/syntenin ...

Liquid jets and bouncing balls combine for surprising results

2013-01-04
A new study published in the American Institute of Physics' (AIP) journal Physics of Fluids reveals that the normal rebounding of a ball changes when it is partially filled with a liquid. Unlike an empty sphere or a solid rubber ball, which both rebound in a classical and well-understood fashion, a fluid-filled ball has its second bounce remarkably cut short. A team of researchers from Brigham Young University in Provo, Utah, uncovered this phenomenon when they investigated what would happen if a sphere were partially filled with a liquid and how that would affect the way ...

Power spintronics: Producing AC voltages by manipulating magnetic fields

2013-01-04
Scientists are putting a new spin on their approach to generating electrical current by harnessing a recently identified electromotive force known as spinmotive force, which is related to the field of spintronics that addresses such challenges as improving data storage in computers. Now, a novel application of spintronics is the highly efficient and direct conversion of magnetic energy to electric voltage by using magnetic nanostructures and manipulating the dynamics of magnetization. According to a report published in the American Institute of Physics' (AIP) journal Applied ...

UC Davis study links low wages with hypertension, especially for women and younger workers

2013-01-04
(SACRAMENTO, Calif.) — Workers earning the lowest wages have a higher risk of hypertension than workers with the highest wages, according to new research from UC Davis. The correlation between wages and hypertension was especially strong among women and persons between the ages of 25 to 44. "We were surprised that low wages were such a strong risk factor for two populations not typically associated with hypertension, which is more often linked with being older and male," said J. Paul Leigh, senior author of the study and professor of public health sciences at UC Davis. ...

Sorting stem cells

2013-01-04
When an embryonic stem cell is in the first stage of its development it has the potential to grow into any type of cell in the body, a state scientists call undifferentiated. A team of researchers from Scotland has now demonstrated a way to easily distinguish undifferentiated embryonic stem cells from later-stage stem cells whose fate is sealed. The results are published in the American Institute of Physics' (AIP) journal Biomicrofluidics. The researchers used an electric field to pull stem cells through a fluid in a process called dielectrophoresis. They varied the frequency ...

New understanding of nerve damage caused by spinal cord injury could improve treatment design

New understanding of nerve damage caused by spinal cord injury could improve treatment design
2013-01-04
New Rochelle, NY, January 3, 2013—More than half of traumatic spinal cord injuries (SCI) in humans are cervical lesions, resulting in chronic loss of limb function. A better understanding of the link between the neurologic damage caused by SCI, spontaneous motor function recovery, and long-term motor deficits would lead to better therapeutic approaches, as discussed in an article in Journal of Neurotrauma, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Journal of Neurotrauma website at http://www.liebertpub.com/neu. About ...

Carbon in Vesta's craters

Carbon in Vestas craters
2013-01-04
The protoplanet Vesta has been witness to an eventful past: images taken by the framing camera onboard NASA's space probe Dawn show two enormous craters in the southern hemisphere. The images were obtained during Dawn's year-long visit to Vesta that ended in September 2012. These huge impacts not only altered Vesta's shape, but also its surface composition. Scientists under the lead of the Max Planck Institute for Solar System Research in Katlenburg-Lindau in Germany have shown that impacting small asteroids delivered dark, carbonaceous material to the protoplanet. In the ...

Planets abound

Planets abound
2013-01-04
PASADENA, Calif.—Look up at the night sky and you'll see stars, sure. But you're also seeing planets—billions and billions of them. At least. That's the conclusion of a new study by astronomers at the California Institute of Technology (Caltech) that provides yet more evidence that planetary systems are the cosmic norm. The team made their estimate while analyzing planets orbiting a star called Kepler-32—planets that are representative, they say, of the vast majority in the galaxy and thus serve as a perfect case study for understanding how most planets form. "There's ...

LAST 30 PRESS RELEASES:

Andrew E. Place, MD, PhD appointed as Dana-Farber/Boston Children’s Cancer and Blood Disorders Center Vice President, Pediatric Chief Medical Officer

COVID-19 antibody discovery could explain long COVID

Wild plants face viral surprise

Storing electrons from hydrogen for clean chemical reactions

Unlocking how to use mRNA to target Alzheimer’s disease

Kessler Foundation secures $770,000 in grants to advance leading-edge spinal cord research

Going ‘back to the future’ to forecast the fate of a dead Florida coral reef

How extratropical ocean-atmosphere interactions can contribute to the variability of jet streams in the Northern Hemisphere

MSK Research Highlights, March 28, 2024

USDA, Nueta Hidatsa Sahnish College collaborate to support Indigenous Seed Sovereignty

For younger women, mental health now may predict heart health later

Missed opportunity: AEDs near cardiac arrests rarely used by bystanders

Eggs may not be bad for your heart after all

Alcohol raises heart disease risk, particularly among women

TTUHSC announces new center for nursing research

Adding just enough fuel to the fire

Impact of synbiotic supplements on the gut microbiome and overall health of penguins

Promising advances in organosilica membranes for separating organic liquid mixtures

Cell phone video technology unveils new method for analyzing walking and gait

Ancient isolation’s impact on modern ecology

Synaptic protein change during development offers clues on evolution and disease

How commercial rooftop solar power could bring affordable clean energy to low-income homes

Taking a closer look at pulmonary fibrosis genetics

Cats with MDR1 mutation at risk of severe reactions to popular medication

IOP Publishing and IPEM mandate reporting of sex and gender in research 

Dogs trained to detect trauma stress by smelling humans’ breath

Electronic device thermal management made simpler and slightly better!

Study: Dangerous surgical site infections can be reduced with simple prevention protocol

Genetic testing of patients with atrial fibrillation can alert clinicians to potential development of life-threatening conditions

Artificial Intelligence tool successfully predicts fatal heart rhythm

[Press-News.org] Editing the genome with high precision
New method allows scientists to insert multiple genes in specific locations, delete defective genes