Tag Archives: DNA

How To Detect Genetic Mutations In Minutes

A team of engineers at the UC Berkeley and the Keck Graduate Institute (KGI) of The Claremont Colleges combined CRISPR with electronic transistors made from graphene to create a new hand-held device that can detect specific genetic mutations in a matter of minutes.

The device, dubbed CRISPR-Chip, could be used to rapidly diagnose genetic diseases or to evaluate the accuracy of gene-editing techniques. The team used the device to identify genetic mutations in DNA samples from Duchenne muscular dystrophy patients.

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We have developed the first transistor that uses CRISPR to search your genome for potential mutations,” said Kiana Aran, an assistant professor at KGI who conceived of the technology while a postdoctoral scholar in UC Berkeley bioengineering professor Irina Conboy’s lab. “You just put your purified DNA sample on the chip, allow CRISPR to do the search and the graphene transistor reports the result of this search in minutes.”

Aran, who developed this technology and brought it to fruition at KGI, is the senior author of a paper describing the device that appears online March 25 in the journal Nature Biomedical Engineering.

Doctors and geneticists can now sequence DNA to pinpoint genetic mutations underlying a host of traits and conditions, and companies like 23andMe and AncestryDNA even make these tests available to curious consumers.

Source: https://news.berkeley.edu/

Molecular Nanocomputers

Computer scientists at Caltech have designed DNA molecules that can carry out reprogrammable computations, for the first time creating so-called algorithmic self-assembly in which the same “hardware” can be configured to run differentsoftware.”

A team headed by Caltech‘s Erik Winfree (PhD ’98), professor of computer science, computation and neural systems, and bioengineering, showed how the DNA computations could execute six-bit algorithms that perform simple tasks. The system is analogous to a computer, but instead of using transistors and diodes, it uses molecules to represent a six-bit binary number (for example, 011001) as input, during computation, and as output. One such algorithm determines whether the number of 1-bits in the input is odd or even, (the example above would be odd, since it has three 1-bits); while another determines whether the input is a palindrome; and yet another generates random numbers.

Think of them as nano apps,” says Damien Woods, professor of computer science at Maynooth University near Dublin, Ireland, and one of two lead authors of the study. “The ability to run any type of software program without having to change the hardware is what allowed computers to become so useful. We are implementing that idea in molecules, essentially embedding an algorithm within chemistry to control chemical processes.”

The system works by self-assembly: small, specially designed DNA strands stick together to build a logic circuit while simultaneously executing the circuit algorithm. Starting with the original six bits that represent the input, the system adds row after row of molecules—progressively running the algorithm. Modern digital electronic computers use electricity flowing through circuits to manipulate information; here, the rows of DNA strands sticking together perform the computation. The end result is a test tube filled with billions of completed algorithms, each one resembling a knitted scarf of DNA, representing a readout of the computation. The pattern on each “scarf” gives you the solution to the algorithm that you were running. The system can be reprogrammed to run a different algorithm by simply selecting a different subset of strands from the roughly 700 that constitute the system.

We were surprised by the versatility of programs we were able to design, despite being limited to six-bit inputs,” says David Doty, fellow lead author and assistant professor of computer science at the University of California, Davis. “When we began experiments, we had only designed three programs. But once we started using the system, we realized just how much potential it has. It was the same excitement we felt the first time we programmed a computer, and we became intensely curious about what else these strands could do. By the end, we had designed and run a total of 21 circuits.”

The findings have been reported in the journal Nature.

Source: https://www.caltech.edu/

‘Epigenetic’ Gene Tweaks Could Trigger Cancer

You could be forgiven for thinking of cancer as a genetic disease. Sure, we know it can be triggered by things you do – smoking being the classic example – but most of us probably assume that we get cancer because of a genetic mutation – a glitch in our DNA. It turns out that this is not quite the end of the story.

We now have the first direct evidence that switching off certain genes – something that can be caused by our lifestyle or the environment we live in – can trigger tumours, without mutating the DNA itself. The good news is that these changes are, in theory, reversible.

All cells contain the same DNA, but individual genes in any cell can be switched on or off by the addition or subtraction of a methyl group – a process known as epigenetic methylation.

For years, researchers have known that mutations to our DNA – either those passed on at birth or those acquired as a result of exposure to radiation, for example – can cause cancer. But epigenetic changes have also been implicated in cancer because abnormal patterns of gene methylation are seen in virtually all types of human tumours.

For example, a gene called MLH1 produces a protein that repairs DNA damage. It is often mutated in colon cancer tumours, but in some tumour samples the gene is healthy, but appears to have been silenced by methylationThe problem is that it has been difficult to test whether abnormal methylation occurs as a result of a tumour or is a cause of its growth.

In genetics you can easily delete a gene and see what the consequence is, but it’s much harder to direct methylation to specific regions of the genome,” says Lanlan Shen of Baylor College of Medicine in Houston, Texas.

To get round this problem, Shen and her colleagues used a naturally occurring sequence of DNA, which draws in methyl groups to methylate nearby genes. They call it their “methylation magnet”.

The team inserted this sequence next to the tumour suppressor gene, p16, in mouse embryonic stem cells. These embryos then developed into mice that carry the “methylation magnet” in all of their cells. The team focused on methylating p16 because it is abnormally methylated in numerous cancers.

They monitored the rodents for 18 months – until they reached the mouse equivalent of middle age. Over this time, 30 per cent of the mice developed tumours around their body, including in their liver, colon, lungs and spleen. None of a control group of genetically identical mice developed tumours.

Some tissues showed faster methylation than others, for example in the liver, colon and spleen, and that’s exactly where we saw the tumours grow,” says Shen. “It seems like methylation predisposed the tissue to tumour development.” She reckons that methylation silences p16, which lifts the break that it normally places on any abnormal cell division.

Source: https://www.newscientist.com/

Have China’s CRISPR Twins Enhanced Brains?

New research suggests that a controversial gene-editing experiment to make children resistant to HIV may also have enhanced their ability to learn and form memories. The twins, called Lulu and Nana, reportedly had their genes modified before birth by a Chinese scientific team using the new editing tool CRISPR. The goal was to make the girls immune to infection by HIV, the virus that causes AIDS. Now, new research shows that the same alteration introduced into the girls’ DNA, deletion of a gene called CCR5, not only makes mice smarter but also improves human brain recovery after stroke, and could be linked to greater success in school.

The answer is likely yes, it did affect their brains,” says Alcino J. Silva, a neurobiologist at the University of California, Los Angeles, whose lab uncovered a major new role for the CCR5 gene in memory and the brain’s ability to form new connections.

“The simplest interpretation is that those mutations will probably have an impact on cognitive function in the twins,” says Silva. He says the exact effect on the girls’ cognition is impossible to predict, and “that is why it should not be done.”

The Chinese team, led by He Jiankui of the Southern University of Science and Technology in Shenzhen, claimed it used CRISPR to delete CCR5 from human embryos, some of which were later used to create pregnanciesHIV requires the CCR5 gene to enter human blood cells.

The experiment has been widely condemned as irresponsible, and He is under investigation in China. News of the first gene-edited babies also inflamed speculation about whether CRISPR technology could one day be used to create super-intelligent humans, perhaps as part of a biotechnology race between the US and China.

There is no evidence that He actually set out to modify the twins’ intelligence. MIT Technology Review contacted scientists studying the effects of CCR5 on cognition, and they say the Chinese scientist never reached out to them, as he did to others from whom he hoped to get scientific advice or support.
As far as I know, we never heard from him,” says Miou Zhou, a professor at the Western University of Health Sciences in California.

Although He never consulted the brain researchers, the Chinese scientist was certainly aware of the link between CCR5 and cognition.  It was first shown in 2016 by Zhou and Silva, who found that removing the gene from mice significantly improved their memory. The team had looked at more than 140 different genetic alterations to find which made mice smarter.

Source: https://www.technologyreview.com/

Sharpen Molecular Scissors And Expand The Gene Editing Toolbox

Wake Forest Institute for Regenerative Medicine (WFIRM) scientists have figured out a better way to deliver a DNA editing tool to shorten the presence of the editor proteins in the cells in what they describe as a “hit and run” approach.

CRISPR (clustered regularly interspaced short palindromic repeats) technology is used to alter DNA sequences and modify gene function. CRISPR/Cas9 is an enzyme that is used like a pair of scissors to cut two strands of DNA at a specific location to add, remove or repair bits of DNA. But CRISPR/Cas9 is not 100 percent accurate and could potentially cut unexpected locations, causing unwanted results.

One of the major challenges of CRISPR/Cas9 mRNA technologies is the possibility of off-targets which may cause tumors or mutations,” said Baisong Lu, Ph.D, assistant professor of regenerative medicine at WFIRM and one of the lead authors of the paper. Although other types of lentivirus-like bionanoparticles (LVLPs) have been described for delivering proteins or mRNAs, Lu said, “the LVLP we developed has unique features which will make it a useful tool in the expanding genome editing toolbox.

To address the inaccuracy issue, WFIRM researchers asked the question: Is there a way to efficiently deliver Cas9 activity but achieve transient expression of genome editing proteins? They tested various strategies and then took the best properties of two widely used delivery vehicles – lentivirus vector and nanoparticles – and combined them, creating a system that efficiently packages Cas9 mRNA into LVLPs, enabling transient expression and highly efficient editing.

Lentiviral vector is a widely used gene delivery vehicle in research labs and is already widely used for delivering the CRISPR/Cas9 mRNA technology for efficient genome editing. Nanoparticles are also being used but they are not as efficient in delivery of CRISPR/Cas9.

By combining the transient expression feature of nanoparticle-delivery strategies while retaining the transduction efficiency of lentiviral vectors, we have created a system that may be used for packaging various editor protein mRNA for genome editing in a ‘hit and run’ manner,” said Anthony Atala, M.D., director of WFIRM and co-lead author of the paper. “This system will not only improve safety but also avoid possible immune response to the editor proteins, which could improve in vivo gene editing efficiency which will be useful in research and clinical applications.

The WFIRM team published its findings in a paper published recently in the journal  Nucleic Acids Research.

Source: https://school.wakehealth.edu/

How To Use The Body’s Inbuilt Healing System

Imperial researchers have developed a new bioinspired material that interacts with surrounding tissues to promote healing. Materials are widely used to help heal wounds: Collagen sponges help treat burns and pressure sores, and scaffold-like implants are used to repair broken bones. However, the process of tissue repair changes over time, so scientists are looking to biomaterials that interact with tissues as healing takes place.

Now, Dr Ben Almquist and his team at Imperial College London have created a new molecule that could change the way traditional materials work with the body. Known as traction force-activated payloads (TrAPs), their method lets materials talk to the body’s natural repair systems to drive healing.

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The researchers say incorporating TrAPs into existing medical materials could revolutionise the way injuries are treated.

Our technology could help launch a new generation of materials that actively work with tissues to drive healing,” said Dr Almquist, from mperial’s Department of Bioengineering.
After an injury, cells ‘crawl’ through the collagen ‘scaffolds’ found in wounds, like spiders navigating webs. As they move, they pull on the scaffold, which activates hidden healing proteins that begin to repair injured tissue. The researchers in the study designed TrAPs as a way to recreate this natural healing method. They folded the DNA segments into three-dimensional shapes known as aptamers that cling tightly to proteins. Then, they attached a customisable ‘handle’ that cells can grab onto on one end, before attaching the opposite end to a scaffold such as collagen.
During laboratory testing of their technique, they found that cells pulled on the TrAPs as they crawled through the collagen scaffolds. The researchers tailor TrAPs to release specific therapeutic proteins based on which cells are present at a given point in time.

This is the first time scientists have activated healing proteins using differing cell types in man-made materials. The technique mimics healing methods found in nature. “Creatures from sea sponges to humans use cell movement to activate healing. Our approach mimics this by using the different cell varieties in wounds to drive healing,” explains Dr Almquist.”

This approach is adaptable to different cell types, so could be used in a variety of injuries such as fractured bones, scar tissue after heart attacks, and damaged nerves. New techniques are also desperately needed for patients whose wounds won’t heal despite current interventions, like diabetic foot ulcers, which are the leading cause of non-traumatic lower leg amputationsTrAPs are relatively straightforward to create and are fully man-made, meaning they are easily recreated in different labs and can be scaled up to industrial quantities.

TrAPs could harness the body’s natural healing powers to repair bone

TrAPs provide a flexible method of actively communicating with wounds, as well as key instructions when and where they are needed. This intelligent healing is useful during every phase of the healing process, has the potential to increase the body’s chance to recover, and has far-reaching uses on many different types of wounds. This technology could serve as a conductor of wound repair, orchestrating different cells over time to work together to heal damaged tissues,” said Dr Almquist.

The findings are published in Advanced Materials.

Source: https://www.imperial.ac.uk/

How To Shrink Objects To The Nanoscale

MIT researchers have invented a way to fabricate nanoscale 3-D objects of nearly any shape. They can also pattern the objects with a variety of useful materials, including metals, quantum dots, and DNA.

MIT engineers have devised a way to create 3-D nanoscale objects by patterning a larger structure with a laser and then shrinking it. This image shows a complex structure prior to shrinking.

It’s a way of putting nearly any kind of material into a 3-D pattern with nanoscale precision,” says Edward Boyden, the Y. Eva Tan Professor in Neurotechnology and an associate professor of biological engineering and of brain and cognitive sciences at MIT. Using the new technique, the researchers can create any shape and structure they want by patterning a polymer scaffold with a laser. After attaching other useful materials to the scaffold, they shrink it, generating structures one thousandth the volume of the original.

These tiny structures could have applications in many fields, from optics to medicine to robotics, the researchers say. The technique uses equipment that many biology and materials science labs already have, making it widely accessible for researchers who want to try it. Boyden, who is also a member of MIT’s Media Lab, McGovern Institute for Brain Research, and Koch Institute for Integrative Cancer Research, is one of the senior authors of the paper, which appears in the Dec. 13 issue of Science. The other senior author is Adam Marblestone, a Media Lab research affiliate, and the paper’s lead authors are graduate students Daniel Oran and Samuel Rodriques.

As they did for expansion microscopy, the researchers used a very absorbent material made of polyacrylate, commonly found in diapers, as the scaffold for their nanofabrication process. The scaffold is bathed in a solution that contains molecules of fluorescein, which attach to the scaffold when they are activated by laser light.

Using two-photon microscopy, which allows for precise targeting of points deep within a structure, the researchers attach fluorescein molecules to specific locations within the gel. The fluorescein molecules act as anchors that can bind to other types of molecules that the researchers add.

You attach the anchors where you want with light, and later you can attach whatever you want to the anchors,” Boyden says. “It could be a quantum dot, it could be a piece of DNA, it could be a gold nanoparticle.” “It’s a bit like film photography — a latent image is formed by exposing a sensitive material in a gel to light. Then, you can develop that latent image into a real image by attaching another material, silver, afterwards. In this way implosion fabrication can create all sorts of structures, including gradients, unconnected structures, and multimaterial patterns,” Oran explains.

Source: http://news.mit.edu/

 

Gene-editing Tools Will Alter Foods Precisely And Cheaply

The next generation of biotech food is headed for the grocery aisles, and first up may be salad dressings or granola bars made with soybean oil genetically tweaked to be good for your heart. By early next year, the first foods from plants or animals that had their DNAedited” are expected to begin selling. It’s a different technology than today’s controversial “genetically modifiedfoods, more like faster breeding that promises to boost nutrition, spur crop growth, and make farm animals hardier and fruits and vegetables last longer.

The U.S. National Academy of Sciences has declared gene editing one of the breakthroughs needed to improve food production so the world can feed billions more people amid a changing climate. Yet governments are wrestling with how to regulate this powerful new tool. And after years of confusion and rancor, will shoppers accept gene-edited foods or view them as GMOs in disguise?

GMOs, or genetically modified organisms, are plants or animals that were mixed with another species’ DNA to introduce a specific trait — meaning they’re “transgenic.” Best known are corn and soybeans mixed with bacterial genes for built-in resistance to pests or weed killers.

If the consumer sees the benefit, I think they’ll embrace the products and worry less about the technology,” said Dan Voytas, a University of Minnesota professor and chief science officer for Calyxt Inc., which edited soybeans to make the oil heart-healthy.

Researchers are pursuing more ambitious changes: Wheat with triple the usual fiber, or that’s low in gluten. Mushrooms that don’t brown, and better-producing tomatoes. Drought-tolerant corn, and rice that no longer absorbs soil pollution as it grows. Dairy cows that don’t need to undergo painful de-horning, and pigs immune to a dangerous virus that can sweep through herds.

Scientists even hope gene editing eventually could save species from being wiped out by devastating diseases like citrus greening, a so far unstoppable infection that’s destroying Florida’s famed oranges. First they must find genes that could make a new generation of trees immune.

If we can go in and edit the gene, change the DNA sequence ever so slightly by one or two letters, potentially we’d have a way to defeat this disease,” said Fred Gmitter, a geneticist at the University of Florida Citrus Research and Education Center, as he examined diseased trees in a grove near Fort Meade.

Source: https://whyy.org/

Mapping Genes Of All Complex Life On Earth

In an effort to protect and preserve the Earth’s biodiversity and kick-start an inclusive bio-economy, the World Economic Forum have announced a landmark partnership between the Earth BioGenome Project, chaired by Harris Lewin, distinguished professor at the University of California, Davis, and the Earth Bank of Codes to map the DNA of all life on Earth. The announcement was made at the 48th World Economic Forum Annual Meeting in Davos-Klosters, Switzerland.

The Earth Biogenome Project aims to sequence the DNA of all the planet’s eukaryotessome 1.5 million known species including all known plants, animals and single-celled organisms. The ambitious project will take 10 years to complete and cost an estimated $4.7 billion. Of the estimated 15 million eukaryotic species, only 10 percent have been taxonomically classified. Of that percentage, scientists have sequenced the genomes of around 15,000 species, less than 0.1 percent of all life on Earth.

The partnership will construct a global biology infrastructure project to sequence life on the planet to enable solutions for preserving the Earth’s biodiversity, managing ecosystems, spawning bio-based industries and sustaining human societies,” said Lewin, who chairs the Earth BioGenome Project working group. Lewin holds appointments in the Department of Evolution and Ecology and the UC Davis Genome Center.

Source: https://www.universityofcalifornia.edu/

Creating Nanocages With Tunable Properties From DNA

How to create nanocages, i.e., robust and stable objects with regular voids and tunable properties? Short segments of DNA molecules are perfect candidates for the controllable design of novel complex structures. Physicists from the University of Vienna, the Technical University of Vienna, the Foschungszentrum Jülich in Germany and Cornell University in the U.S.A., investigated methodologies to synthesize DNA-based dendrimers in the lab and to predict their behavior using detailed computer simulations.

Nanocages are highly interesting molecular constructs, from the point of view of both fundamental science and possible applications. The cavities of these nanometer-sized objects can be employed as carriers of smaller molecules, which is of critical importance in medicine for drug or gene delivery in living organisms. This idea brought together researchers from various interdisciplinary fields who have been investigating dendrimers as promising candidates for creating such nano-carriers. Their tree-like architecture and step-wise growth with repeating self-similar units results in dendrimers containing cavities, hollow objects with controllable design.

The researchers found a way to create dendrimers rigid enough to prevent back-folding of outer arms even in the case of high branching generations, preserving regular voids in their interior. The nanocages they created, in the lab and studied computationally are DNA-based dendrimers, or so-called, dendrimer-like DNAs (DL-DNA).

Their results are published in the journal Nanoscale.

Source: https://medienportal.univie.ac.at/