In BriefResearchers from UC San Diego's School of Medicine have tested a modified CRISPR-Cas9 technique designed to target RNA instead of DNA. Rcas9 could potentially improve the lives of patients with ALS, Huntington's disease, or myotonic dystrophy by delaying the progression of their disorders.

The most efficient and effective gene-editing tool in use today is CRISPR-Cas9. Just this year, researchers have successfully used it fora wide variety of experiments, from modifying garden vegetables to encoding a GIF in bacterial DNA. Most recently, the tool was used to remove a genetic disease from a human embryo.

Although undeniably powerful, CRISPR-Cas9 does have its limitations; it can only target DNA. To extend its capabilities to includeRNA editing, researchers from the University of California San Diego (UCSD) School of Medicinedeveloped amodification of CRISPR, and theyre calling their toolRNA-targeting Cas9 (RCas9).

In a study published in Cell, the UCSD team tested their technique by correcting the kinds of molecular mistakes that cause people to develop microsatellite repeat expansion diseases, such ashereditary amyotrophic lateral sclerosis (ALS)and Huntingtons disease.

During standard CRISPR-CAs9 gene editing, a guide RNA is instructed to deliver a Cas9 enzyme to a specific DNA molecule. The researchers from UCSD instead instructed it to target an RNA molecule.

Tests conducted in the laboratory showed that RCas9 removed 95 percent ofproblem-causing RNA for myotonic dystrophy types 1 and 2, Huntingtons disease, and one type of ALS. The technique also reversed 93 percent of the dysfunctional RNA targets in the muscle cells of patients with myotonic dystrophy type 1, resulting in healthier cells.

This is exciting because were not only targeting the root cause of diseases for which there are no current therapies to delay progression, but weve re-engineered the CRISPR-Cas9 system in a way thats feasible to deliver it to specific tissues via a viral vector, senior author Gene Yeo, a cellular and molecular medicine professor at UCSD School of Medicine, explained in a press release.

Across the globe, an estimated 450,000 patients are said to be living with ALS. Roughly 30,000 of those are from the U.S. where 5,600 people are diagnosed with the diseases every year. The exact number of Huntingtons disease cases, however, isnt quite as easy to pin down. One estimate says that around 30,000 Americans display symptoms of it, while more than 200,000 are at risk.

Regardless of the exact numbers, these two neurological diseases clearly affect a significant number of people. This prevalence and the absence of a known curemakes the UCSD teams research all the more relevant. Even more exciting is the fact that the same kinds of RNA mutations targeted by this study are known to cause more than 20 other genetic diseases.

Our ability to program the RCas9 system to target different repeats, combined with low risk of off-target effects, is its major strength, co-first author of the study Ranjan Batra said in the UCSD press release.

However, the researchers do know that what theyve accomplished is just a first step. While RCas9 works in a lab, they still have to figure out how it will fare when tested in actual patients.

The main thing we dont know yet is whether or not the viral vectors that deliver RCas9 to cells would elicit an immune response, explained Yeo. Before this could be tested in humans, we would need to test it in animal models, determine potential toxicities, and evaluate long-term exposure.

Ultimately, while RCas9 couldnt exactly deliver a cure, it could potentially extend patients healthy years. For disease like ALS and Huntingtons, thats a good place to start.

Read the rest here:
A New Gene Editing Technique Could Finally Allow Us to Treat ALS - Futurism

Dr. Steven Powell. Credit: Sanford Health

Sanford Health is the first site in the United States to launch a clinical trial using a genetically-engineered virus that aims to destroy therapy-resistant tumors.

The Phase I immunotherapy trial is for those ages 18 and older with metastatic solid tumors that have not responded to standard treatments. The treatment injects an oncolytic (cancer-destroying) virusvesicular stomatitis virus (VSV)into the tumor. The virus is engineered to grow in cancer cells, destroy these tumors, and then spread to other cancer sites. During this process, it recruits the immune system to the area with the goal of triggering an immune response.

The virus, commonly known as VSV, can infect cattle, but it rarely causes serious infections in humans.

The virus is genetically altered by adding two genes. The first gene is a human interferon beta gene, which is a natural anti-viral protein. This protects the normal, healthy cells from being infected, while still allowing the virus to work against cancer cells.

The second gene makes the NIS protein found in the thyroid gland, which allows the researchers to track the virus as it spreads to tumor sites. Vyriad, a biopharmaceutical company in Rochester, Minnesota, developed this technology and is led by Stephen Russell, M.D., Ph.D., a professor of molecular medicine at the Mayo Clinic and an expert in oncolytic virus therapy.

"Oncolytic viruses are the next wave of promising cancer immunotherapy treatments," says Dr. Steven Powell, a medical oncologist with the Sanford Cancer Center in Sioux Falls, S.D., who collaborated with Vyriad on the development of this clinical trial. "We are very excited about using VSV as researchers have seen promising results using other similar viruses, such as the polio virus, in early clinical trials."

Dr. Shannon Peck, an interventional radiologist at Sanford with experience in interventional therapeutics, oversees the viral injection procedures. Enrollees in the trial are given a one-time injection and then are followed for 43 days to evaluate for safety and clinical benefit. To ensure safety during this period, other anti-cancer therapies cannot be used. However, after this 43-day period, chemotherapy, immunotherapy or targeted therapy can be restarted.

Sanford Health is the first in the nation to launch the Vyriad solid tumor oncolytic virus clinical trial. Call 1-877-SURVIVAL to learn more or to see if you qualify.

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Clinical trial uses a genetically engineered virus to fight cancer - Medical Xpress

More than 300,000 students return to college and university campuses this month in Georgia.

The biggest changes include a newcampus carry law that allows students with licensed weapons permits to carry firearms on portions of campuses, additional credit to studentswho take approved STEM courses to keep their HOPE scholarships and the repurposing of Turner Field into Georgia States new football stadium.

Heres a look at some changes at some of metro Atlantas largest campuses and the University of Georgia.

The renovation of Rebekah Scott Hall. The $16.5 million project will house a new welcome center, updated offices for admissions and financial aid and residential space for students who will live on the upper two floors.

Atlanta Metropolitan State College

An online Bachelor of Science degree in organizational leadership. It includes a choice of concentration in public service, healthcare administration or office administration and technology.

Its createdthe Department of Cyber-Physical Systems. It will include new bachelor of science programs in cybersecurity, robotics, and data analytics.

The first-two floors of a new $400 million hospital tower opened on July 31, bringing the total number of licensed beds at Emory University Hospital to 733. Patient floors begin opening in late August, and the hospital tower will be fully operational by the end of October.

Awidening of a portion of Clifton Road and its sidewalks, a bike lane, new landscaping and improved visibility of intersections along Clifton Road.

The campus West Village, which includes five micro-restaurants, Panera Bread and Starbucks, music classrooms, and shared meeting rooms.

Georgia Techs West Village, which will include shops, restaurants, classrooms and meeting rooms. PHOTO CONTRIBUTED

The new football stadium, which will have its first game on Aug. 31 against Tennessee State.

A new College of the Arts that offers 20 top undergraduate, graduate and non-degree programs in art, design, music, film, digital media, theater, etc.

New building for its growing Creative Media Industries Initiative.

Kennesaw State University

Students applying to KSU for fall 2018 can choose to apply through a non-binding, early action application or through a regular decision application, a process used by most competitive universities in the state. Meeting the minimum requirements will no longer guarantee a spot at the university.

New degree programs in computer engineering and cybersecurity.

The college is expanding its health science classes. For the first time, classes in human anatomy, microbiology and ethnobotany will be offered this fall to attract more students interested in pursuing careers as dentists, pharmacists, and medical doctors.

Interim president Harold Martin, a former valedictorian. The college is conducting a search process for a permanent president.

The university is breaking ground on the I.W.Ike Cousins for Science and Innovation. The center will have laboratory-classrooms, independent study labs, open study rooms and faculty offices.

The college has a new documentary filmmaking and photography majors beginning this fall. Both new majors are part of the Department of Art & Visual Culture, formerly the Department of Art & Art History.

In September, theyll open a facility to support the Center for Molecular Medicine. The state provided $17 million to support the project. The faculty for this center are working on cures and therapies for diseases such as diabetes, cancer and dementia.

Best quality of life: Emory University (No. 3), Agnes Scott College (No. 20) Great financial aid: Emory University (No. 15) Most conservative students: Berry College (No. 20) Most liberal students: Agnes Scott College (No. 12) Most LGBTQ-friendly: Agnes Scott College (No. 7) Lots of race/class interaction: Agnes Scott College (No. 20) Most beautiful campus: Berry College (No. 9) Most active student government: Agnes Scott College (No. 9) Best college dorms: Emory University (No. 8) Most religious students

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Georgia colleges gear up for new semester - AJC.com - Atlanta Journal Constitution

The researchers discovered that the genetic activity of mouse skeletal muscles is particularly intense during the first two weeks after birth; a number of genes alter the amount of proteins produced, while other genes go through alternative splicing and produce different proteins.

Among the genes going through alternative splicing, those involved in calcium-handling functions predominated. Calcium is very important for skeletal and heart muscle because the influx of calcium into the cell stimulates contraction and other functions.

First author Dr. Amy Brinegar, who was a graduate student in the Cooper lab while she was working on this project and recently graduated from the doctoral program in molecular and cellular biology at Baylor, selected three calcineurin A genes, which are involved in calcium-handling functions, and reversed their natural process of alternative splicing in adult mouse muscles. Then, Dr. George Rodney, associate professor of molecular physiology at Baylor, and a graduate student in his lab, James Loehr, who are co-authors on this paper, determined the effect of switching back alternative splicing on functions of isolated adult mouse skeletal muscle in the lab.

They discovered that muscles in which the adult forms of the calcineurin A genes had been switched back to the newborn forms showed a change in calcium flow and were less strong than muscles that retained the adult forms of calcineurin A.

We showed that just by changing three of about 11,000 genes that are estimated to be expressed in adult mouse muscle, we were able to change physiological parameters of those muscles, said Brinegar. This work supports the growing evidence in favor of a physiological role of alternative splicing.

Importantly, about 50 percent of the genes we discovered to undergo alternative splicing are conserved, meaning that the genes go through the same changes both in mice and humans, which opens the possibility of modeling human muscle disorders in the mouse, Cooper said.

Other contributors top this work include Zheng Xia and Wei Li, both from Baylor.

Financial support was provided by National Institutes of Health grants R01AR045653, R01HL045565, R01AR060733, T32 HL007676, R01HG007538, R01CA193466 and R01AR061370. Further support was provided by the Muscular Dystrophy Association grant RG4205.

See original here:
Change in protein production essential to muscle function - Baylor College of Medicine News (press release)

Researchers say they've found a system in the human heart that allows the organ to restart itself. Their discovery could lead to the replacement of pacemakers.

In an episode of Star Trek: The Next Generation, Lt. Worf is badly injured, but recovers when it is discovered that his body holds a lot of redundant parts and organs for example, 23 ribs that allow him to regenerate.

Science fiction?

Not entirely.

A team of researchers at The Ohio State University Wexner Medical Center discovered that the human heart contains its own fail-safe backup battery system to regulate the heartbeat.

Their findings were published in Science Translational Medicine.

If further testing is successful, fewer people might need mechanical pacemakers in the future.

The potential market is big.

More than 200,000 people in the United States have a pacemaker implanted every year.

The research is still preliminary, but scientists hope to turn it into practical use some day.

In the future we want to develop something that practitioners would welcome, Vadim Fedorov, PhD, an associate professor of physiology and cell biology at The Ohio State University College of Medicine, told Healthline.

Fedorov explained that an implanted pacemaker works by replacing the hearts defective natural pacemaker functions.

The sinoatrial (SA) node, or sinus node, is the heart's natural pacemaker. It's a small mass of specialized cells in the top of the right atrium (upper chamber of the heart). It produces the electrical impulses that cause the heart to beat.

The heart is hardwired to maintain consistency. Irregular heartbeat, or arrhythmia, can be due to heart disease or other problems, such as changes in diet or hormones or electrolyte imbalance.

Optical and molecular mapping of the human heart revealed that the SA node is home to multiple pacemakers, specialized cardiomyocytes that generate electrical heartbeat-inducing impulses.

Total cardiac arrest occurs only when all pacemakers and conduction pathways fail.

Too technical?

Think of it as a car battery. One day your car wont start. Turns out the battery is still good, but one of the connector cables is bad.

So you clean or replace the wire and save yourself from major repairs.

The Ohio State teams discovery showed that the human heart battery restarts itself.

To prove their point, the researchers actually restarted hearts that were destined for the trash heap.

Most of them came from people getting new hearts or accident victims whose hearts were not suitable for transplant.

We kept them in a special solution, he said. When we warm them to body temperature, they will beat.

The discovery, while exciting, is not going to change clinical practice in the next 60 days.

But it offers promise.

Dr. John Hummel, FACC, is a cardiologist at The Ohio State University Wexner Medical Center and is director of the electrophysiology research section and professor of cardiovascular medicine.

He told Healthline the study is intriguing.

These findings finally give us insight as to the actual structure and behavior of the natural pacemaker of the human heart, he said. Diagnosing disease of the natural pacemaker is often straightforward, but can also be one of the more challenging diagnoses to make.

Dr. Fedorovs findings will likely allow us to develop new approaches to discriminate disease from normal behavior of the sinus node, and give our patients a definitive diagnosis of health or disease of the hearts natural pacemaker, Hummel explained.

Funding to translation of this bench research to clinic research is the next step, he added.

Dr. Gordon Tomaselli, professor of medicine, cellular and molecular medicine at the Johns Hopkins School of Medicine and past president of the American Heart Association, expressed similar thoughts.

The work by Vadim Fedorovs group is a beautifully done study on explanted [not used for transplant] human hearts, Tomaselli told Healthline.

He called the infrared optical mapping studies with pharmacological interventions demonstrating the functional redundancy and complexity of the sinoatrial node (SAN) the most compelling part of the work.

Being able to view the hearts in three dimensions increases the researchs usefulness.

Tomaselli pointed out that researchers have known for decades from previous work in animals, and in clinical human electrophysiological labs, that SAN is functionally redundant and anatomically complex.

He urged caution.

I do not think this paper will fundamentally change the management of patients with regard to pacemaker implantation, he said. Although around half of pacemakers are implanted for diseases of the sinus node or atrium, they are implanted not to prolong life but instead to relieve symptoms [fatigue, shortness of breath particularly with exercise].

He went on, The more life-threatening problems with electrical conduction in the heart for which we put in pacemakers to prolong life involve the electrical system that connects the top and bottom chamber [called the AV node] and the conduction system in the lower chambers. This paper does not address this problem.

So, for the meantime, a Klingon skeleton might be your best bet.

Read this article:
The Human Heart May Have a Natural 'Backup Battery' - Healthline

By KIMBERLY HOUGHTONUnion Leader CorrespondentAugust 14. 2017 11:06PM

This sequence of images shows the development of embryos after being injected with a biological kit to edit their DNA, removing a genetic mutation known to cause hypertrophic cardiomyopathy.(Oregon Health & Science University)

Bryan Luikart, an associate professor of molecular and systems biology at Geisel School of Medicine at Dartmouth College.

It is pretty amazing. It is a super-exciting time to be a scientist right now, said Bryan Luikart, an associate professor of molecular and systems biology at Geisel School of Medicine at Dartmouth College.

The study, which was published in the journal Nature, was detailed in a New York Times report. According to the article, Oregon researchers reported they repaired dozens of human embryos, fixing a mutation that causes a common heart condition that can lead to sudden death later in life.

The way they have dodged some ethical considerations is that they didnt go on to have that embryo grow into a person, said Luikart, explaining that if the embryos with the repaired mutation did have the opportunity to develop, they would be free of the heart condition.

At the Geisel School of Medicine at Dartmouth, Luikart and his colleagues have already been using this concept with mouse embryos, focusing specifically on autism.

Researchers are using the gene-editing method called CRISPR-Cas9 in hopes of trying to more fully understand autism, which he said is the most critical step in eventually finding a cure.

I think the CRISPR is a tremendous breakthrough. The question really is where and when do you want to use it, Luikart said. I have no ethical concerns using it as a tool to better understand biology.

The new milestone, an example of human genetic engineering, does carry ethical concerns that Luikart said will trigger some debates. He acknowledged that while the advancement of gene-editing technology could eventually stop unwanted hereditary conditions, it also allows for creating babies with smarter, stronger or more attractive traits.

The ability to do that is now within our grasp more than it has ever been, he said.

More importantly, the breakthrough could ultimately eliminate diseases, Luikart said. As the technology advances, he said, genetic diseases that are passed down to children may be corrected before the child receives them.

He used another example of a brain tumor, which often returns after it is surgically removed. Now, once the brain tumor is removed, there is the possibility of placing something in the space to edit and fix the mutation that causes the brain tumor in the first place if physicians are able to find the right cell to edit, Luikart said.

People are definitely thinking along those lines, or cutting the HIV genome, said Luikart, who predicts that those advancements will occur in mice within the next decade, and the ability to do that in humans is definitely there.

The big question is whether that can occur without some sort of side effect that was not predicted, he said.

Columbia University Medical Center posted an article earlier this year warning that CRISPR gene editing can cause hundreds of unintended mutations, based on a study published recently in Nature Methods.

This past May, MilliporeSigma announced it has developed a new genome editing tool that makes CRISPR more efficient, flexible and specific, giving researchers more experimental options and faster results that can accelerate drug development and access to new therapies, according to a release.

CRISPR genome editing technology is advancing treatment options for some of the toughest medical conditions faced today, including chronic illnesses and cancers for which there are limited or no treatment options, states the release, adding the applications of CRISPR are far ranging from identifying genes associated with cancer to reversing mutations that cause blindness.

It is pretty big news, Luikart said.

khoughton@newstote.com

HealthHanover

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New Hampshire biologist reacts to gene-editing discovery - The Union Leader

Credit: CC0 Public Domain

Researchers have developed a more precise way of diagnosing suicide risk, by developing blood tests that work in everybody, as well as more personalized blood tests for different subtypes of suicidality that they have newly identified, and for different psychiatric high-risk groups.

The research team, led by scientists at the Indiana University School of Medicine, also showed how two apps, one based on a suicide risk checklist and the other on a scale for measuring feelings of anxiety and depression, work along with the blood tests to enhance the precision of tests and to suggest lifestyle, psychotherapeutic and other interventions. Lastly, they identified a series of medications and natural substances that could be developed for preventing suicide.

"Our work provides a basis for precision medicine and scientific wellness preventive approaches," said Alexander B. Niculescu III, MD, PhD, professor of psychiatry and medical neuroscience at IU School of Medicine and attending psychiatrist and research and development investigator at the Richard L. Roudebush Veterans Affairs Medical Center.

The article, "Precision medicine for suicidality: from universality to subtypes and personalization," appears in the August 15 online edition of the Nature Publishing Group's leading journal in psychiatry, Molecular Psychiatry.

The research builds on earlier studies from the Niculescu group.

"Suicide strikes people in all walks of life. We believe such tragedies can be averted. This landmark larger study breaks new ground, as well as reproduces in larger numbers of individuals some of our earlier findings," said Dr. Niculescu.

There were multiple steps to the research, starting with serial blood tests taken from 66 people who had been diagnosed with psychiatric disorders, followed over time, and who had at least one instance in which they reported a significant change in their level of suicidal thinking from one testing visit to the next. The candidate gene expression biomarkers that best tracked suicidality in each individual and across individuals were then prioritized using the Niculescu group's Convergent Functional Genomics approach, based on all the prior evidence in the field.

Next, working with the Marion County (Indianapolis, Ind.) Coroner's Office, the researchers tested the validity of the biomarkers using blood samples drawn from 45 people who had committed suicide.

The biomarkers were then tested in another larger, completely independent group of individuals to determine how well they could predict which of them would report intense suicidal thoughts or would be hospitalized for suicide attempts.

The biomarkers identified by the research are RNA molecules whose levels in the blood changed in concert with changes in the levels of suicidal thoughts experienced by the patients. Among the findings reported in the current paper were:

Explore further: Researchers identify objective predictors of suicidality in women

More information: Molecular Psychiatry (2017). DOI: 10.1038/mp.2017.128

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Precision medicine opens the door to scientific wellness preventive approaches to suicide - Medical Xpress