Archive for the ‘Gene Therapy Research’ Category

GRAND RAPIDS, MI An international research effort led by a Van Andel Institute scientist has identified several new genes frequently mutated in bile duct cancer, a deadly form of liver cancer.

The breakthrough came after two years of intensive research that involved scientists visiting villagers in northern Thailand, an area with a high rate of bile duct cancer, according to VAI officials.

The research was led by Bin Tean Teh, the director of the Van Andel Research Institutes Translational Cancer Research Laboratory at the National Cancer Center in Singapore.

According to a statement released by VAI, bile duct cancer accounts for 10 to 25 percent of all primary liver cancers worldwide and has a poor prognosis, the VAI says. The high incidence in Thailand is attributed to consumption of raw fish infected with parasites, called liver flukes. The flukes cause infection in the bile duct and eventually cause cancer.

The researchers analyzed bile duct cancers of Thai patients and discovered mutations in 187 genes. They focused on 15 genes that were frequently mutated.

This discovery adds depth to what we currently know about bile duct cancer, Teh said in VAIs statement. More important is that we are now aware of new genes and their effects on bile duct cancer, and we now need to further examine their biological aspects to determine how they bring about the onset of cholangiocarcinoma (bile duct cancer).

We are talking about the potential to save many lives in Thailand, said Professor Vajarabhongsa Bhudhisawasdi, director of bile duct cancer research at Khon Kaen University of Thailand.

The research findings are published online in Nature Genetics.

Email Sue Thoms at sthoms1@mlive.com and follow her on Twitter at twitter.com/suethoms

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Van Andel Institute leads breakthrough research into deadly form of liver cancer

SAN DIEGO, May 16, 2012 /PRNewswire/ -- Cardium Therapeutics (CXM) today announced a late-breaking poster presentation at the American Society of Gene & Cell Therapy (ASGCT) 15th Annual Meeting being held May 16-19, 2012 at the Pennsylvania Convention Center in Philadelphia, PA.

(Photo: http://photos.prnewswire.com/prnh/20120516/LA07787)

(Logo: http://photos.prnewswire.com/prnh/20051018/CARDIUMLOGO)

The new research findings demonstrate that cardiac ischemia plays an important role in adenovector gene transfection (delivery) in mammalian hearts. Based on this understanding, using a standard balloon angioplasty catheter, researchers have developed and tested a new method to induce transient ischemia during a non-surgical interventional cardiac procedure, which when coupled with the infusion of nitroglycerin, boosts the delivery (cell transfection) of an adenovector gene construct into heart cells. The increase in adenovector-based gene transfection with the new technique is over two orders of magnitude (>100 fold).

Cardium's new method of adenovector delivery takes advantage of the findings that transient ischemia appears to alter the permeability barrier of the vascular endothelium and may expose the blood to the coxsackie-adenovirus receptor mediating adenovector uptake by the heart. Balloon angioplasty catheters have been used for many years to dilate blocked coronary arteries, sometimes with use of a stent, and these catheters have also been used safely by cardiologists in patients with coronary artery disease to study the effects of brief ischemia. Cardium's new technique inflates the balloon in non-narrowed areas, and only enough to briefly interrupt flow using inflation pressure that is less than that used for performing angioplasty.

Cardium's recently initiated Russian-based ASPIRE Phase 3 / registration clinical study uses transient ischemia techniques during non-surgical percutaneous catheterization with a standard angioplasty catheter together with the intracoronary infusion of nitroglycerin with the Generx [Ad5FGF-4] product candidate for the treatment of patients with myocardial ischemia and stable angina pectoris. These patients have atherosclerotic coronary artery disease, and the Company's Generx product candidate is intended to stimulate the growth of new or additional collateral blood vessels to bypass blockages.

These studies were conducted at Emory University School of Medicine, led by Jakob Vinten-Johnasen, PhD., and co-sponsored by a Small Business Innovative Research grant from the National Institutes of Health (Cardium Therapeutics) and the Carlyle Fraser Heart Center (Emory). At the conference Gabor M. Rubanyi, MD, PhD, Cardium's Chief Scientific Officer, will present the late-breaking poster entitled "Transient Ischemia is Necessary for Efficient Adenovector Gene Transfer in the Heart", on May 17, 2012 from 3:00 to 5:30 p.m. in Exhibit Hall A. The poster presentation can be viewed at http://www.cardiumthx.com/pdf/Generx-ASGCT-Poster-Presentation-May-2012.pdf.

In addition, Dr. Rubanyi will also make an oral presentation titled: "New Perspectives for Angiogenic Gene Therapy to Treat Myocardial Ischemia in Patients with Coronary Disease" to attendees at the ASGCT Meeting today, May 16. The presentation will provide a historical overview of the Generx clinical development program and how these new and important preclinical findings have been incorporated into the protocol for the 100-patient Generx ASPIRE Phase 3 registration study which was recently initiated in the Russian Federation for patients with myocardial ischemia and stable angina pectoris. The presentation is now available for viewing at http://www.cardiumthx.com/pdf/Generx-ASGCT-May-2012-Rubanyi.pdf.

About Generx and the ASPIRE Study

Generx (Ad5FGF-4) is a disease-modifying regenerative medicine biologic that is being developed to offer a one-time, non-surgical option for the treatment of myocardial ischemia in patients with stable angina due to coronary artery disease, who might otherwise require surgical and mechanical interventions, such as coronary artery by-pass surgery or balloon angioplasty and stents. Similar to surgical/mechanical revascularization approaches, the goal of Cardium's Generx product candidate is to improve blood flow to the heart muscle but to do so non-surgically, following a single administration from a standard balloon angioplasty catheter. The video "Cardium Generx Cardio-Chant" provides an overview Generx and can be viewed at http://www.youtube.com/watch?v=pjUndFhJkjM.

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Cardium Reports New Catheter-Based Methods Significantly Boost Cardiac Gene Delivery In Late-Breaking Presentation at ...

ScienceDaily (May 16, 2012) A well-known genetic risk factor for Alzheimer's disease triggers a cascade of signaling that ultimately results in leaky blood vessels in the brain, allowing toxic substances to pour into brain tissue in large amounts, scientists report May 16 in the journal Nature.

The results come from a team of scientists investigating why a gene called ApoE4 makes people more prone to developing Alzheimer's. People who carry two copies of the gene have roughly eight to 10 times the risk of getting Alzheimer's disease than people who do not.

A team of scientists from the University of Rochester, the University of Southern California, and other institutions found that ApoE4 works through cyclophilin A, a well-known bad actor in the cardiovascular system, causing inflammation in atherosclerosis and other conditions. The team found that cyclophilin A opens the gates to the brain assault seen in Alzheimer's.

"We are beginning to understand much more about how ApoE4 may be contributing to Alzheimer's disease," said Robert Bell, Ph.D., the post-doctoral associate at Rochester who is first author of the paper. "In the presence of ApoE4, increased cyclophilin A causes a breakdown of the cells lining the blood vessels in Alzheimer's disease in the same way it does in cardiovascular disease or abdominal aneurysm. This establishes a new vascular target to fight Alzheimer's disease."

The team found that ApoE4 makes it more likely that cyclophilin A will accumulate in large amounts in cells that help maintain the blood-brain barrier, a network of tightly bound cells that line the insides of blood vessels in the brain and carefully regulates what substances are allowed to enter and exit brain tissue.

ApoE4 creates a cascade of molecular signaling that weakens the barrier, causing blood vessels to become leaky. This makes it more likely that toxic substances will leak from the vessels into the brain, damaging cells like neurons and reducing blood flow dramatically by choking off blood vessels.

Doctors have long known that the changes in the brain seen in Alzheimer's patients -- the death of crucial brain cells called neurons -- begins happening years or even decades before symptoms appear. The steps described in Nature discuss events much earlier in the disease process.

The idea that vascular problems are at the heart of Alzheimer's disease is one championed for more than two decades by Berislav Zlokovic, M.D., Ph.D., the leader of the team and a neuroscientist formerly with the University of Rochester Medical Center and now at USC. For 20 years, Zlokovic has investigated how blood flow in the brain is affected in people with the disease, and how the blood-brain barrier allows nutrients to pass into the brain, and harmful substances to exit the brain.

At Rochester, Zlokovic struck up a collaboration with Bradford Berk, M.D., Ph.D.,a cardiologist and CEO of the Medical Center. For more than two decades Berk has studied cyclophilin A, showing how it promotes destructive forces in blood vessels and how it's central to the forces that contribute to cardiovascular diseases like atherosclerosis and heart attack.

"As a cardiologist, I've been interested in understanding the role of cyclophilin A in patients who suffer from cardiovascular illness," said Berk, a professor at the Aab Cardiovascular Research Institute. "Now our collaboration in Rochester has resulted in the discovery that it also has an important role in Alzheimer's disease. The finding reinforces the basic research enterprise -- you never know when knowledge gained in one area will turn out to be crucial in another."

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Alzheimer's gene causes brain's blood vessels to leak toxins and die

Public release date: 16-May-2012 [ | E-mail | Share ]

Contact: Tom Rickey tom_rickey@urmc.rochester.edu 585-275-7954 University of Rochester Medical Center

A well-known genetic risk factor for Alzheimer's disease triggers a cascade of signaling that ultimately results in leaky blood vessels in the brain, allowing toxic substances to pour into brain tissue in large amounts, scientists report May 16 in the journal Nature.

The results come from a team of scientists investigating why a gene called ApoE4 makes people more prone to developing Alzheimer's. People who carry two copies of the gene have roughly eight to 10 times the risk of getting Alzheimer's disease than people who do not.

A team of scientists from the University of Rochester, the University of Southern California, and other institutions found that ApoE4 works through cyclophilin A, a well-known bad actor in the cardiovascular system, causing inflammation in atherosclerosis and other conditions. The team found that cyclophilin A opens the gates to the brain assault seen in Alzheimer's.

"We are beginning to understand much more about how ApoE4 may be contributing to Alzheimer's disease," said Robert Bell, Ph.D., the post-doctoral associate at Rochester who is first author of the paper. "In the presence of ApoE4, increased cyclophilin A causes a breakdown of the cells lining the blood vessels in Alzheimer's disease in the same way it does in cardiovascular disease or abdominal aneurysm. This establishes a new vascular target to fight Alzheimer's disease."

The team found that ApoE4 makes it more likely that cyclophilin A will accumulate in large amounts in cells that help maintain the blood-brain barrier, a network of tightly bound cells that line the insides of blood vessels in the brain and carefully regulates what substances are allowed to enter and exit brain tissue.

ApoE4 creates a cascade of molecular signaling that weakens the barrier, causing blood vessels to become leaky. This makes it more likely that toxic substances will leak from the vessels into the brain, damaging cells like neurons and reducing blood flow dramatically by choking off blood vessels.

Doctors have long known that the changes in the brain seen in Alzheimer's patients the death of crucial brain cells called neurons begins happening years or even decades before symptoms appear. The steps described in Nature discuss events much earlier in the disease process.

The idea that vascular problems are at the heart of Alzheimer's disease is one championed for more than two decades by Berislav Zlokovic, M.D., Ph.D., the leader of the team and a neuroscientist formerly with the University of Rochester Medical Center and now at USC. For 20 years, Zlokovic has investigated how blood flow in the brain is affected in people with the disease, and how the blood-brain barrier allows nutrients to pass into the brain, and harmful substances to exit the brain.

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Alzheimer's gene causes brain's blood vessels to leak, die

Public release date: 16-May-2012 [ | E-mail | Share ]

Contact: Cathia Falvey cfalvey@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, May 16, 2012The inaugural issue of BioResearch Open Access, a new bimonthly peer-reviewed open access journal, was released today by Mary Ann Liebert, Inc., publishers. The Journal provides a new rapid-publication forum for a broad range of scientific topics including but not limited to molecular and cellular biology, tissue engineering and biomaterials, regenerative medicine, stem cells, gene therapy, systems biology, genetics, biochemistry, virology, microbiology, and neuroscience. The first issue is available on the BioResearch Open Access website at http://www.liebertpub.com/biores.

The premier issue includes research papers and a brief report from the U.S., U.K., Germany, and Korea on diverse topics such as tissue engineering, stem cells, HIV, and genetics. Forthcoming papers for the second issue include genetics, xenotransplantation, nuclear transfer, and cardiac research.

The Journal is under the leadership of Editor-in-Chief Jane Taylor, PhD, Senior Research Fellow, MRC Centre for Regenerative Medicine, University of Edinburgh, and seasoned journal editors as Section Editors, including James M. Wilson, MD, PhD, University of Pennsylvania; Antonios G. Mikos, PhD, Rice University; Professor Sir Ian Wilmut, OBE FRS FRSE, University of Edinburgh; Peter C. Johnson, MD, Scintellix, LLC, Raleigh, NC; Aubrey D.N.J. de Grey, PhD, SENS Foundation, Cambridge, UK; Alan J. Russell, PhD, Carnegie Mellon University; Thomas Hope, PhD, Northwestern University; Ganes C. Sen, PhD, Cleveland Clinic Foundation; Bruce A. Sullenger, PhD, Duke University Medical Center; Graham C. Parker, PhD, Wayne State University School of Medicine; Carol Shoshkes Reiss, PhD, New York University; Stephen C. Ekker, PhD, Mayo Clinic, Rochester, MN; John B. West, MD, PhD, University of California, San Diego; David L. Woodland, PhD, Chief Scientific Officer, Keystone Symposia on Molecular and Cellular Biology; Stephen Higgs, PhD, Kansas State University; Eugene Kolker, PhD, Seattle Children's Hospital; and Domenico Grasso, PhD, PE, DEE, University of Vermont.

The Journal welcomes basic science and translational research in the form of original research articles, comprehensive review articles, mini-reviews, rapid communications, brief reports, technical reports, hypothesis articles, perspectives, and letters to the editor. All articles in BioResearch Open Access will be published online within 4 weeks of acceptance. Articles will be fully open access and posted on PubMedCentral. All articles submitted through July 15, 2012 will be made open access without article processing charges. BioResearch Open Access is fully NIH-, HHMI-, and Wellcome Trust compliant.

"BioResearch Open Access is a fully refereed multidisciplinary journal and provides all the checks and balances that rigorous peer review ensures," says Mary Ann Liebert, president of Mary Ann Liebert, Inc., publishers. "An outstanding editorial team comprised of experienced journal editors guarantees the integrity of the Journal."

###

About the Publisher

Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Tissue Engineering, Human Gene Therapy, Nucleic Acid Therapeutics, Stem Cells and Development, Viral Immunology, DNA and Cell Biology, and Antioxidants & Redox Signaling. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 70 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc. website at http://www.liebertpub.com.

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Premier issue of BioResearch Open Access launched by Mary Ann Liebert Inc. publishers

Viruses act as tiny piezoelectric generators

Viruses, tiny chunks of protein and nucleic acid, have long plagued mankind and its evolutionary ancestors before it. But thanks to the wonders of modern genetic engineering, researchers believe they have finally been able to instill a beneficial purpose in these deadly pests.

I. From Pest to Power

A team of researchers at Lawrence Berkeley National Laboratory -- one of 16 U.S. Department of Energy (DOE) national laboratories -- has created a special breed of virus that undergoes self-nanoassembly to form tiny piezoelectric generators -- machines which harvest mechanical energy (vibrations or pressure) to directly produce electricity.

The special "bug" is the M13 bacteriophage, a rod-shaped virus that only infects bacteria (such asE. coli bacteria)-- not humans.

Faculty researchersSeung-Wuk Lee, Ramamoorthy Ramesh, and Byung Yang Lee selected the virus due to its tendency to self-assemble into nanofilms, given its rod-like shape. The viruses tightly pack "like chopsticks in a box" and are easy to grow by the millions given a small supply of host bacteria.

II. Refining the Virus

But the effect was too weak to be of use. So the researchers spliced a quadruplet of negatively charged amino acids into one of the coat proteins. The results was a larger voltage gradient across the coat. The researchers also tested stacking films of the modifed viruses to see how thick they could layer the viruses in order to get the maximum effect.

When pressure was applied to the film a 400 millivolt, 6 nanoampere current was put off. That's about a quarter of the voltage of an AAA battery, albeit at a far smaller current. Still it was enough to power a '1' to show up on a low-power liquid crystal display.

Read this article:
Berkeley Trains "Harmless" Viruses to Harvest Human Kinetic Energy

Researchers may be closing in on diseases inherited component

Web edition : Tuesday, May 15th, 2012

Schizophrenias elusive genetic roots may finally be within grasp. A new, wide-ranging effort has uncovered a set of DNA signatures that are shared by people with the disease consistently enough that the set can be used to reliably predict whether someone has the disease. If replicated, the results may point out ways to diagnose schizophrenia and suggest new targets for treatment.

By analyzing a battery of 542 genetic variants, researchers could predict who had schizophrenia in a group of European Americans and African Americans. The confirmation of the result in people of varying ancestry suggests that the set of genes truly does detect the core features of the disorder, scientists report online May 15 in Molecular Psychiatry.

Genetic studies in psychiatry tend to produce initial excitement but are then not reproduced in independent populations, which is the most important proof that a finding is solid and real, says study coauthor Alexander Niculescu of the Indiana University School of Medicine in Indianapolis.

Niculescu and his colleagues created their gene panel by assessing a slew of earlier studies on schizophrenia: Data from humans and animals on gene variation and gene behavior all fed into the teams analysis. If a gene popped out of several different datasets, the reasoning went, it is probably important to schizophrenia. Niculescu compares this method called convergent functional genomics to an Internet search: The more links to a web page, the higher it comes up on your search list.

After sifting through all of this data, the team identified some top candidates, some already known to be related to schizophrenia (DISC1, a known culprit, sits at the top of the list) and a handful that have never before been linked to the disease.

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Schizophrenia’s core genetic features proposed

Public release date: 14-May-2012 [ | E-mail | Share ]

Contact: Jim Dryden jdryden@wustl.edu 314-286-0110 Washington University School of Medicine

Researchers at Washington University School of Medicine in St. Louis have developed a genetic test that can accurately predict whether the most common form of eye cancer will spread to other parts of the body, particularly the liver.

In 459 patients with ocular melanoma at 12 centers in the United States and Canada, the researchers found the test could successfully classify tumors more than 97 percent of the time.

The study will appear in an upcoming issue of the journal Ophthalmology, but is now online.

"When the cancer spreads beyond the eye, it's unlikely any therapy is going to be effective," says principal investigator J. William Harbour, MD. "But it's very possible that we can develop treatments to slow the growth of metastatic tumors. The real importance of this test is that by identifying the type of tumor a patient has, we can first remove the tumor from the eye with surgery or radiation and then get those individuals at high risk into clinical trials that might be able to help them live longer."

Harbour believes the test should allow ocular oncologists to quickly evaluate the risks associated with particular tumors and to begin treatment the moment they can detect any spread of the cancer.

Melanoma of the eye is relatively rare, diagnosed in about 2,000 people in the United States each year. Advances in treatment have allowed surgeons to preserve patients' vision, but when cancer spreads beyond the eye, it often is deadly.

About a decade ago, Harbour, the Paul A. Cibis Distinguished Professor of Ophthalmology and Visual Sciences, began using gene expression profiling to monitor the activity of thousands of genes in and around ocular melanoma tumors.

"At the time, we were surprised to see that based on these gene expression profiles, the tumors clustered into two groups that corresponded, almost perfectly, to patients whose cancer spread and those whose cancer was confined within the eye," says Harbour, who directs Washington University's Center for Ocular Oncology. "Tumors with a class 1 gene expression profile, or 'signature,' very rarely spread, but those with a class 2 profile frequently develop into metastatic cancer."

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Genetic test identifies eye cancer tumors likely to spread

In households across the country, children conceived with donated sperm are struggling with serious genetic conditions inherited from men they have never met: heart defects, spinal muscular atrophy, neurofibromatosis type 1 and fragile-X syndrome the most common form of mental retardation in boys and others.

Donated eggs pose a risk as well, but the threat of genetic harm from sperm donation is arguably much greater. Sperm donors are no more likely to carry genetic diseases than anybody else, but they can father a far greater number of children: 50, 100 or even 150, each a potential inheritor of flawed genes.

Sharine and Brian Kretchmar of Yukon, Okla., tried a number of medical treatments to conceive a second child.

After a depressing series of failures, they were advised by a doctor to find a sperm donor. For more than a year, the Kretchmars researched sperm banks and donors. The donor they chose was a family man, a Christian like them, they were told. Most important, he had a clean bill of health. So the Kretchmars jumped in. After artificial insemination, Sharine Kretchmar became pregnant, and in April 2010, she gave birth to a boy they named Jaxon.

But the baby failed to have a bowel movement in the first day or so after birth, a sign to doctors that something was wrong. Doctors returned with terrible news: Jaxon appeared to have cystic fibrosis.

"We were pretty much devastated," Sharine Kretchmar said.

Genetic testing showed that Jaxon did carry the genes for cystic fibrosis. Sharine Kretchmar, 33, had no idea she was a carrier and was shocked to discover that so, too, was the Kretchmars' donor.

His sperm, they would discover, was decades old, originally donated at a laboratory halfway across the country and frozen ever since. Whether it was properly tested is a matter of dispute.

Experience not unique

Sadly, the Kretchmars' experience is not unique.

Read more here:
Given number of inheritors, donor sperm carries risk of genetic harm

Every few days my Google Alerts have been dropping in my inbox reviews of Harry Osters Legacy: A Genetic History of the Jewish People. The latest, is in the The Tablet, A Case for Genetic Jewishness:

For a Jewish genetics researcher, being told inprintthat Hitler would certainly have been very pleased by your work cant be pleasant. But thats what happened in 2010 toHarry Ostrer, a geneticist at the Albert Einstein College of Medicine, when he and his colleagues published astudyshowing that Jews in three different geographical areas had certain collections of genes that made them more biologically similar to one another than they were to non-Jews in the same regions. The work also showed that Jews around the world could trace their ancestry to a group of people who lived in the Middle East 2,000 years ago; that meant, however, that certain genetic signatures could be used to identify Jews, indicating that Jews share a common biological identity beyond their religious affiliationwhich is what inspired the Hitler crack.

I dont plan on reading Legacy because I already read the paper which it is based on, Abrahams Children in the Genome Era: Major Jewish Diaspora Populations Comprise Distinct Genetic Clusters with Shared Middle Eastern Ancestry. It is now open access, so you can read it too. As implied in the article in The Tablet the biggest finding in this paper is that most of the worlds Jewry seem to share tracts of the genome which are identical by descent (IBD). You dont have to be a geneticist to intuit that being IBD implies relatively recent and elevated shared descent from a common set of ancestors. In particular the authors were looking for segments of the genome where individuals shared the same sequence of genetic markers. Very long sequences indicate a relatively recent common ancestor, while many short ones suggest more distant but numerous common ancestors.

From looking at these patterns of relatedness the authors infer that despite the genetic variation in the modern Jewry, most of the worlds Jews, from Iran to Morocco to Lithuania, share common ancestry from a source population which flourished ~2,500 years ago. All that being said, genetics is only part of the puzzle here. In the discussion the authors suggest that Yet, the sharing of Iranian and Iraqi Jews of a branch on the phylogenetic tree with the Adygei suggests that a certain degree of admixture may have occurred with local populations not included in this study. I argue in my post The Assyrians and Jews: 3,000 years of common history, a clear and distinct category of Jew as opposed to generic North Levantine in the year 500 BC probably does not make biological sense, though it might make culturally sense (and generic North Levantine is obviously not accurate, as most of these individuals had strong tribal or ethnic identities at the time). Finally, I dont think I highlighted in my earlier commentary that these data imply that the rise of Christianity and Islam fundamentally stabilized the genetics of the Jewish people, insofar as much of the admixture upon the core base in the peripheral populations seems to predate the rise of these religious civilizaitons. Once Christianity and Islam marginalized the Jews, the gene flow from non-Jews to Jews diminished greatly. This is curiously analogous to the cultural involution which Jews also underwent during this period.

Read more from the original source:
Abraham’s genetic threads | Gene Expression

Cancer Genetics is pursuing a strategy that differs from Facebook's IPO plan, expert says.

A Rutherford, N.J.-based start-up developing tools to diagnose cancer is planning to launch an initial public offering this week under the long shadow of Facebook's long-awaited blockbuster IPO.

Cancer Genetics Inc. is looking to raise more than $50 million with an initial public offering of 4 million shares priced between $11 to $13 a share.

The offering comes as the IPO market is struggling back toward its pre-recession level of activity, although it remains well below the peak of the dot-com fueled boom of the 1990s. If Cancer Genetics prices this week, it will be the first IPO in North Jersey since Park Ridge-based SeaCube Container Leasing Ltd. went public in October 2010. The ticker symbol would be CGIX, and the shares would trade on the Nasdaq Stock Market.

How the Facebook IPO will affect that of Cancer Genetics is unclear. David Menlow, president of IPOfinancial.com, said he thinks it "greatly hampers their chance of success."

"Investors are not interested in paying attention to anything other than the 800-ton gorilla in the room," which is Facebook, he said.

But Jay R. Ritter, a professor of finance at University of Florida in Gainesville, who tracks IPOs, said the two companies are playing to different investors.

Cancer Genetics, which is planning its IPO for Friday, is looking to attract institutional investors interested in holding company stock for the long period it takes for a biotech company to make a medical breakthrough, he said. In contrast, many Facebook investors are mainly interested in the chance of making a quick profit if the stock takes off, he said.

"Facebook is getting huge amounts of attention," Ritter said. "Lots of investors are coming out of the woodwork who do not have an interest in buying biomedical companies."

Cancer Genetics, founded in 1999, is focused on developing and commercializing tests and services to diagnose, predict and help treat hematological, urogenital and HPV-associated cancers. The top executives at Cancer Genetics are Chairman Raju S.K. Chaganti, Chief Executive Officer Panna L. Sharma and Elizabeth A. Czerepak, chief financial officer.

Originally posted here:
Cancer Genetics IPO Faces Facebook

WESTMINSTER, Colo., May 16, 2012 /PRNewswire/ -- GeneThera, Inc. (GTHR.PK) announced today that Applied Genetics, GeneThera's majority owned subsidiary, signed a research and test validation agreement with Universidad National Autonoma de Mexico (UNAM). Scope of the agreement is to validate GeneThera proprietary Johne's disease (JD) HerdCheck Field Collection System (FCS) Molecular Assay in Mexico. Dr. Tony Milici, interim president of Applied Genetics and CEO of GeneThera, stated, "This agreement is another major milestone in establishing GeneThera and Applied Genetics' leadership in the field of Johne's disease molecular testing. UNAM's support is of fundamental importance to speed up the validation process of GeneThera's Johne's disease molecular testing, which will lead to JD test approval by the Mexican Government."

Dr. Gilberto Chaves Griz, Professor of Veterinary Pathology, in the Department of Veterinary medicine at UNAM and Director of the Johne's Disease Center, who is one of the world's most renowned expert in the field of Johne's disease declared, "We are very pleased to partner with Applied Genetics and GeneThera to work on this project. It is extremely critical that we can diagnose JD in Mexico using the most advanced technology available. It is also of paramount importance to establish a Johne's disease program at the national level. Mexico has one of the largest cows, goat and sheep populations in Northern and Central America, yet no data exists to the extent of Johne's infection in these animals. It is our firm intention to establish a National Testing Program for Johne's Disease in Mexico with the help of Applied Genetics and GeneThera's state of the art technology." UNAM is the largest University in Mexico. Applied Genetics is a molecular diagnostic company that focuses on commercializing molecular testing for Johne's disease in Mexico.

Johne's disease is a global devastating and incurable disease of dairy cows, sheep and goats caused by a bacterium called Mycobacterium Paratuberculosis sub. Avium, (MAP). Dairy products, contaminated with MAP, are the vehicles by which the infection spreads in the human intestine triggering the onset of Crohn's disease. Applied Genetics employs the use of GeneThera HerdCheck to test and control the spread of Johne's disease in Mexico. HerdCheck is a proprietary molecular diagnostic system based on the use of high throughput robotics and Real time PCR.

About GeneThera, Inc.

GeneThera, Inc. is a molecular biotechnology company located in Westminster, Colorado. The Company's proprietary diagnostic solution is based on a genetic expression system (GES) and Johne's disease management system, HERDCHECK, designed to function on a highly automated Fluorogenic PCR platform. This platform enables GeneThera to offer tests that are presently not available from other technologies. The GES and HERDCHECK systems are designed for a host of individual diseases, the current priority being Johne's disease. For more information, contact Dr. Tony Milici at 720 439-3011.

This press release contains forward-looking statements, which are made pursuant to the Safe-Harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as "intends," "believes," and similar expressions reflecting something other than historical fact are intended to identify forward-looking statements, but are not the exclusive means of identifying such statements. These forward-looking statements involve a number of risks and uncertainties, including the timely development and market acceptance of products and technologies, the ability to secure additional sources of finance, the ability to reduce operating expenses, and other factors described in the Company's filings with the Securities and Exchange Commission. The actual results that the Company achieves may differ materially from any forward-looking statement due to such risks and uncertainties. The Company undertakes no obligation to revise or update any forward-looking statements in order to reflect events or circumstances that may arise after the date of this release.

http://www.genethera.net

The rest is here:
Applied Genetics Signs Agreement With The National University Of Mexico (UNAM)

Recently, there was a gathering of scientists at the Hyatt Regency in Greenwich. They were there to discuss their latest findings in cancer research -- especially in the use of gene therapy in cancer treatment. There was tangible excitement in the room. Among those in attendance was Dr. Carl June of the University of Pennsylvania, who had, using gene therapy, actually eliminated all signs of cancer in two patients he was treating. Also there was Dr. Hui Hu, who works in the same city as June, at the Wistar Institute, and who is having similar success treating mice with cancer with his gene therapy, which he wants to apply to human patients.

The reason for this writing, however, is another reason for the gathering -- the celebration of the 10th anniversary of the Alliance for Cancer Gene Therapy (ACGT), a Greenwich non-profit that has helped fund these scientists and others like them; and the legacy of Ed Netter, of Greenwich, co-founder of ACGT, who died last year, just short of Dr. Carl June's news of his gene therapy treatment.

Barbara Netter, Ed Netter's widow and cofounder of ACGT, was feeling the excitement in the scientific meeting held before the gala dinner honoring her late husband and ACGT.

"We have so much energy now with Carl June," she said. "We're receiving a lot more applications for grants. There's a lot of collaboration and partnering happening."

It was the death of the Netters' daughter-in-law from breast cancer that inspired Ed and Barbara Netter to create ACGT 10 years ago as a vehicle to raise money for research into cancer gene therapy.

"The vision that Ed had is a new way to really get the science into clinical trials that will show the (gene therapy) concept at work," said Barbara Netter.

Last August, Dr. Carl June reported to the world the success of his clinical trial, supported by ACGT, in which he genetically modified the T-cells of three patients with chronic lymphocytic leukemia to target and kill their tumors. Two of the three patients remain cancer free, with the third patient's cancer significantly reduced.

June's treatment, he said, was still only in the first phase. But he's now adding more patients. "We've taken in our first pediatric patient -- a 6-year-old girl with leukemia. She was infused today," June said.

This is the first of 400 patients June wants to treat within the next year or two.

"The gene therapy approach is fundamentally different from current therapies," said June, "and these ideas need to move to human treatment."

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Greenwich couples' legacy lives on in ACGT

Public release date: 16-May-2012 [ | E-mail | Share ]

Contact: John Pastor jdpastor@ufl.edu 352-273-5815 University of Florida

Using gene transfer techniques pioneered by University of Florida faculty, Taiwanese doctors have restored some movement in four children bedridden with a rare, life-threatening neurological disease.

The first-in-humans achievement may also be helpful for more common diseases such as Parkinson's that involve nerve cell damage caused by lack of a crucial molecule in brain tissue. The results are reported today (May 16) in the journal Science Translational Medicine.

The children in the study, who ranged in age from 4 to 6, inherited a rare disease known as aromatic L-amino acid decarboxylase deficiency, or AADC. Patients with AADC are born without an enzyme that enables the brain to produce the neurotransmitter dopamine. They generally die in early childhood.

In a phase 1 clinical trial led by Paul Wuh-Liang Hwu, M.D., of the National Taiwan University Hospital, surgeons used a delivery vehicle called an adeno-associated virus type 2 vector to transport the AADC gene into localized areas of the brains of three girls and a boy.

Before therapy, the children showed practically no spontaneous movement and their upper eyelids continually drooped. After receiving the corrective gene, the children gradually gained some head movement. Sixteen months afterward, the children's weight had increased, one patient was able to stand and the other three were able to sit up without support.

The study shows gene therapy that targets AADC deficiency is well-tolerated and leads to improved motor development and function, according to co-authors Barry Byrne, M.D., Ph.D., director of UF's Powell Gene Therapy Center, and Richard O. Snyder, Ph.D., director of UF's Center of Excellence for Regenerative Health Biotechnology. Both are members of the UF Genetics Institute.

"The children in this study have the most severe form of inherited movement disorder known, and the only treatments so far have been supportive ones," said Byrne, a pediatric cardiologist and associate chairman of the department of pediatrics in the College of Medicine. "It is gratifying to see it is possible to do something to help them, other than providing feeding tubes and keeping them safe. This absolutely opens the door to the possibility of even earlier treatment of neurological diseases by direct gene transfer, and has implications for Parkinson's disease, ALS and even cognitive diseases such as dementia when caused by gene defects."

The Powell Gene Therapy Center provided expertise to the Taiwanese physicians on treating the patients and engineering the corrective gene that spurs production of the absent AADC enzyme. UF's Center of Excellence for Regenerative Health Biotechnology manufactured the vector, packaging genetic material it received from Taiwan into virus particles that were purified, characterized and tested for sterility and stability before being shipped to the clinic for use in patients.

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Children with rare, incurable brain disease improve after gene therapy

ScienceDaily (May 14, 2012) A new study consisting of inducing cells to express telomerase, the enzyme which -- metaphorically -- slows down the biological clock -- was successful. The research provides a "proof-of-principle" that this "feasible and safe" approach can effectively "improve health span."

A number of studies have shown that it is possible to lengthen the average life of individuals of many species, including mammals, by acting on specific genes. To date, however, this has meant altering the animals' genes permanently from the embryonic stage -- an approach impracticable in humans. Researchers at the Spanish National Cancer Research Centre (CNIO), led by its director Maria Blasco, have demonstrated that the mouse lifespan can be extended by the application in adult life of a single treatment acting directly on the animal's genes. And they have done so using gene therapy, a strategy never before employed to combat aging. The therapy has been found to be safe and effective in mice.

The results were recently published in the journal EMBO Molecular Medicine. The CNIO team, in collaboration with Eduard Ayuso and Fatima Bosch of the Centre of Animal Biotechnology and Gene Therapy at the Universitat Autonoma de Barcelona (UAB), treated adult (one-year-old) and aged (two-year-old) mice, with the gene therapy delivering a "rejuvenating" effect in both cases, according to the authors.

Mice treated at the age of one lived longer by 24% on average, and those treated at the age of two, by 13%. The therapy, furthermore, produced an appreciable improvement in the animals' health, delaying the onset of age-related diseases -- like osteoporosis and insulin resistance -- and achieving improved readings on aging indicators like neuromuscular coordination.

The gene therapy consisted of treating the animals with a DNA-modified virus, the viral genes having been replaced by those of the telomerase enzyme, with a key role in aging. Telomerase repairs the extreme ends or tips of chromosomes, known as telomeres, and in doing so slows the cell's and therefore the body's biological clock. When the animal is infected, the virus acts as a vehicle depositing the telomerase gene in the cells.

This study "shows that it is possible to develop a telomerase-based anti-aging gene therapy without increasing the incidence of cancer," the authors affirm. "Aged organisms accumulate damage in their DNA due to telomere shortening, [this study] finds that a gene therapy based on telomerase production can repair or delay this kind of damage," they add.

'Resetting' the biological clock

Telomeres are the caps that protect the end of chromosomes, but they cannot do so indefinitely: each time the cell divides the telomeres get shorter, until they are so short that they lose all functionality. The cell, as a result, stops dividing and ages or dies. Telomerase gets around this by preventing telomeres from shortening or even rebuilding them. What it does, in essence, is stop or reset the cell's biological clock.

But in most cells the telomerase gene is only active before birth; the cells of an adult organism, with few exceptions, have no telomerase. The exceptions in question are adult stem cells and cancer cells, which divide limitlessly and are therefore immortal -- in fact several studies have shown that telomerase expression is the key to the immortality of tumour cells.

It is precisely this risk of promoting tumour development that has set back the investigation of telomerase-based anti-aging therapies.

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First gene therapy successful against aging-associated decline: Mouse lifespan extended up to 24% with a single ...

Philippine Daily Inquirer

Former President and current Pampanga Rep. Gloria Macapagal-Arroyo, who was suffering from a mineral deficiency in her bones arising from two corrective surgeries last September, wanted to seek alternative stem cell therapy abroad.

However, she was barred from leaving the country last November after Justice Secretary Leila de Lima refused to honor the temporary restraining order issued by the high court on the inclusion of Arroyo and her husband Jose Miguel Mike Arroyo in the immigration bureaus watch list.

In the wake of Arroyos supposed plan to try the radical technology at stem cell centers abroad to cure what her doctors here described as a rare bone disease, a province mate and a colleague of the former President filed a bill to put up a stem cell center in the country.

Pampanga Rep. Carmelo F. Lazatin, a member of the minority bloc in Congress, has filed House Bill No. 5287 mandating the establishment of a research facility to explore the benefits of stem cell technology as a potential cure for incurable diseases.

Blank cells

Stem cells, the foundation of every organ, tissue and cell within the human body, are like blank cells that do not yet have a specific physiological function, according to Harvard Stem Cell Institute (HSCI).

But when proper conditions in the body or in the laboratory occur, stem cells develop into specialized tissues and organs, HSCI explains in its website, adding that there are two sources of stem cells used in research: the adult stem cells and embryonic stem cells.

Adult stem cells are found in differentiated tissues and organs throughout the body while embryonic stem cells are obtained from the inner cell mass of a blastocyst, the ball of cells formed when the fertilized egg or zygote divides and forms two cells, then again to form four and so on, HSCI said.

In 2008, the Vatican issued a sweeping document on bioethical issues titled Dignitas Personae or The Dignity of the Person, taking into account recent developments in biomedical technology and reinforcing the Churchs opposition to embryonic stem cell research, in vitro fertilization, human cloning and genetic testing on embryos before implantation.

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In The Know: Stem cell therapy

THE WOODLANDS, Texas--(BUSINESS WIRE)--

Opexa Therapeutics, Inc. (NASDAQ:OPXA - News), a company developing Tovaxin, a novel T-cell therapy for multiple sclerosis (MS), today reported financial results for the quarter ended March 31, 2012 and provided an update on recent corporate developments.

Corporate development highlights include:

We are progressing favorably in the planning and preparations for a clinical trial in Secondary Progressive MS patients, commented Neil K. Warma, President and Chief Executive Officer of Opexa. The clinical trial protocol was submitted to the FDA for final review and we received no additional comments from them. This is a key milestone for us, providing us with the necessary regulatory positioning to advance with the trial preparations and discussions with potential trial sites. Operationally, we believe we remain on track to initiate the trial in the coming months as the team continues to work diligently to finalize preparations. In order to initiate the trial, we will need to secure additional financing, either through a potential partnership or additional capital raise, and this continues to be an important focus for us.

The meeting we recently held with clinical trial investigators at the annual American Academy of Neurology conference was well attended and included some of the most influential MS opinion leaders participating in the discussions related to our clinical trial design and enrollment criteria. We are anticipating strong enrollment once we are able to begin the trial, driven by the support of the clinicians and a strong desire from patients to participate. SPMS is understood to be a very serious medical condition coupled with the fact that patients have limited treatment options. We hope that Tovaxin can eventually develop into a treatment of choice, not only for SPMS but for all MS patients.

As of the end of the first quarter, our cash and cash equivalents totaled approximately $4.7million and our monthly burn rate for the quarter was approximately $810,000, inclusive of increased cash expenditures to support preparations for the initiation of the planned Phase IIb clinical study in North America.

First Quarter Financial Results

Opexa reported no commercial revenues in the three months ended March 31, 2012 or in the comparable prior-year period.

Research and development expenses were $1,490,097 for the three months ended March 31, 2012, compared with $685,161 for the three months ended March 31, 2011. The increase in expenses was primarily related to an increase in the procurement and use of laboratory reagents and supplies, and increases in professional service fees, employee personnel costs, facility costs and non-cash stock compensation expense.

General and administrative expenses for the three months ended March 31, 2012 were $816,196, compared with $592,058 for the three months ended March 31, 2011. The increase in expense is due to increases in business development activities, legal expenses, employee compensation expense and non-cash stock compensation expense.

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Opexa Therapeutics Reports First Quarter 2012 Financial Results and Provides Corporate Update

By Elizabeth Lopatto - Wed May 09 18:00:00 GMT 2012

An experimental therapy that reprograms the immune system then spurs the growth of healthy insulin-producing cells reversed late-stage diabetes in mice and may lead to a cure for people, researchers said.

Mice with Type 1 diabetes, a form of the disease in which the bodys immune system destroys cells that secrete insulin, were free of illness after scientists shut down the immune attack, reprogrammed the errant cells and coaxed the growth of healthy, new insulin-producers. The study was published today in the journal Science Translational Medicine.

About 3 million Americans have Type 1 diabetes, which is usually diagnosed in children, according to the Juvenile Diabetes Research Foundation. The only treatment is insulin injected to replace the bodys naturally-occurring version of the hormone, which is needed to convert blood sugar into energy. The experimental immune system approach appears promising because its the first time diabetes has been cured in mice with advanced disease, said Anita Chong, a medical researcher at the University of Chicago.

Conceptually, each component isnt novel, people have thought about them, but put it together and show it can work? said Chong, who wrote an accompanying editorial to the study. Thats very exciting.

There are many more steps before the treatment will be tested in humans, starting with non-human primate models, she said in a telephone interview.

Type 1 diabetes differs from the more common Type 2 form in that it is an autoimmune disease, in which the immune system kills the cells needed to produce insulin. In Type 2 diabetes, the body produces insulin but cells no longer respond to it.

Diabetics must test their blood sugar several times a day, and sometimes experience hypoglycemia, or dangerously low blood sugar, while they sleep at night.

In the study, the mice were given antibodies to attack two kinds of immune cells that kill the pancreas insulin-producing beta cells. Then the mice had a bone marrow transplant to replenish the vanquished cells. Bone marrow is where blood cells are made, and the transplant let the mice make immune cells that wouldnt attack the beta cells. A treatment with pancreas growth factor spurred creation of new beta cells.

The study was led by Defu Zeng, an endocrinologist at City of Hope medical center in Duarte, California, and funded by the Iacocca Family Foundation, and private donations from Todd and Karen Wanek and the Davis family.

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Immune Cell Therapy Cures Diabetic Mice, Researchers Find

Wed May 9, 2012 3:35pm BST

(Reuters) - Pluristem Therapeutics Inc said a 7-year old girl suffering from a bone marrow disease experienced a reversal of her condition after receiving its experimental stem cell therapy, sending the Israeli company's shares up 32 percent.

The girl, suffering from aplastic bone marrow in which the patient has no blood-forming stem cells, had a significant rise in her red cells, white cells and platelets following an injection of Pluristem's therapy -- PLacental eXpanded cells.

"The results of this unique case indicate that PLX cells may be effective in treating other diseases that affect the bone marrow," Reuven Or, the child's physician at Hadassah Medical Center, was quoted in a statement by Pluristem.

Last September, the company said animal studies showed that the therapy had the potential to treat blood tissue complications related with acute radiation syndrome, commonly called radiation sickness.

Last month, the U.S. health regulators gave a go ahead to the company to start a mid-stage trial of the therapy for treating Intermittent Claudication -- a subset of peripheral artery disease.

Pluristem shares, which have gained 5 percent since receiving the FDA nod for the mid-stage trial, were up 15 percent at $2.70 in morning trade on the Nasdaq. They touched a high of $3.10 earlier.

(Reporting by Esha Dey in Bangalore; Editing by Gopakumar Warrier)

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Pluristem stem cell therapy saves a patient, shares jump

By Kate Rauch on May 11, 2012

Chronic pain affects an estimated 116 million Americans and costs $635 billion each year in medical treatment and lost productivity.

Aditi Bhargava, PhD

Aditi Bhargava, PhD, associate professor at UCSFs School of Medicine, is using a technique known as RNA interference (RNAi) to develop a gene therapy system that sends specific commands to certain neurons, or nerve cells, telling them to turn off pain, or stop inflammation.

The current treatments for pain dull everything, Bhargava said. You have a little fire in the kitchen, but your only solution is a fire hose that floods the entire house. You put out the fire, but youre affecting the whole house in the process a huge negative side effect.

Likening her method to a Trojan horse, Bhargavas novel therapeutic approach essentially hides the pain-silencing commands, carried by distinct proteins that affect cellular function, inside other proteins which bind only to the troublemaker cells. Once attached, they release their hidden power.

We want to target the small or medium neurons that sense pain, while leaving other neurons unaffected, she said. Were hoping that while you reduce pain, for example, youll still be able to chew or not drool.

The data from her proof-of-concept animal studies look promising, Bhargava said. I believe that this project has tremendous translational potential to turn what we learn into concrete benefits for patients.

Targeted pain and inflammation relief could also be used to treat illnesses, such as Inflammatory Bowel Disease (IBD), an autoimmune condition. This approach has potential to not only minimize unwanted side effects, but save costs, as it sends very small amounts of drug therapies to the targeted cells.

Targeted delivery of drug would reduce the dose required to treat, reduce cost, and most importantly, reduce unwanted side effects.

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Targeted Gene Therapy Offers Relief from Pain and Inflammation

09-05-2012 19:22 Humanity faces increasing problems around the supply and quality of water. The dual implications of an ever expanding population, combined with the threat of climate change, makes water a precious commodity. Delving deep into the composition of water however, may help its preservation into the future. In this presentation, Professor Chris Saint will share examples from his research where gene technology has been applied to identify and record microorganisms that cause problems in our water supplies. These include blue-green algae and protozoan parasites such as Cryptosporidium. For the first time DNA tests are being developed to rapidly assess the risk that these organisms present to drinking water consumers. Research has also demonstrated that not all bugs in water are bad -- some can be used to breakdown key pollutants, leading to a possibility of using bacteria to clean up our water supplies. Professor Saint will discuss how these discoveries will lead the way in monitoring water quality, and share his thoughts on what the future holds in this area.

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Christopher Saint - Water quality management - it can be in the genes - Knowledge Works - Video

10-05-2012 04:57 Watch in 1080p or 720p for best experience! I hope you enjoy watching the video. I do not own the music in this video! All rights reserved to DVBBS & Arkasia! Follow Arkasia: Follow DVBBS: Copyright Disclaimer Under Section 107 of the Copyright Act 1976, allowance is made for "fair use" for purposes such as criticism, comment, news reporting, teaching, scholarship, and research. Fair use is a use permitted by copyright statute that might otherwise be infringing. Non-profit, educational or personal use tips the balance in favor of fair use.

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DVBBS - DRVGS ft. Hayley Gene (Arkasia Remix) [Audio React] - Video

Public release date: 10-May-2012 [ | E-mail | Share ]

Contact: Tracey Peake tracey_peake@ncsu.edu 919-515-6142 North Carolina State University

Imagine being able to control genetic expression by flipping a light switch. Researchers at North Carolina State University are using light-activated molecules to turn gene expression on and off. Their method enables greater precision when studying gene function, and could lead to targeted therapies for diseases like cancer.

Triplex-forming oligonucleotides (TFOs) are commonly used molecules that can prevent gene transcription by binding to double-stranded DNA. NC State chemist Dr. Alex Deiters wanted to find a way to more precisely control TFOs, and by extension, the transcription of certain genes. So Deiters attached a light-activated "cage" to a TFO. When exposed to ultraviolet (UV) light, the cage is removed, and the TFO is free to bind with DNA, inhibiting transcription of the gene of interest.

"In the absence of light, transcription activity is 100 percent," says Deiters. "When we turn on the light, we can take it down to about 25 percent, which is a significant reduction in gene expression."

Additionally, Deiters fine-tuned the process by attaching a caged inhibitor strand to the TFO. In the absence of UV light, the TFO behaves normally, binding to DNA and preventing gene expression. However, when exposed to UV light, the caged inhibitor activates and stops the TFO from binding with DNA, turning gene transcription on.

"We've created a tool that allows for the light-activation of genetic transcription," Deiters says. "By giving researchers greater temporal and spatial control over gene expression, we've expanded their ability to study the behavior of particular genes in whichever environment they choose."

###

The research appears online in ACS Chemical Biology, and was funded by the National Institutes of Health. Deiters worked with NC State graduate students Jeane M. Govan, Rajendra Uprety and James Hemphill and Wake Forest University's Mark O. Lively on the research.

Note to editors: An abstract of the paper follows.

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Researchers use light to switch on gene expression

ScienceDaily (May 10, 2012) History, science and discovery come together to help family members affected by this syndrome make informed family planning choices.

C5ORF42 was identified as the gene that causes Joubert Syndrome in a number of families in the Lower St. Lawrence region of Quebec where the causal gene had remained unknown since the initial description of the syndrome in 1969. This is what a study in the April issue of The American Journal of Human Genetics reveals. The study was conducted by researchers from the Sainte-Justine University Hospital Research Center and the Centre of Excellence in Neuromics of Universit de Montral (CENUM).

Joubert Syndrome is a condition that affects brain development and manifests itself through delayed psychomotor development, abnormal coordination of eye movements and respiratory abnormalities. Since Dr. Marie Joubert and her colleagues described it for the first time in 1969, a number of related genes have been identified in various populations, but the causal gene of the Quebec form of the syndrome has remained until now unknown.

"No studies had been done to identify the genetic origin of the disease in Quebec, more specifically in the exact area of the Lower St. Lawrence where most cases in Quebec are concentrated," Dr. Jacques Michaud, the study's principal investigator, explained. "This is the first study to present a picture of Joubert syndrome in the Quebec population. It will allow family members affected by the syndrome to assess their children's genetic risks with a simple DNA test."

The finding is interesting, both genetically and historically, since, while Joubert Syndrome is present around the world, genetic strains can vary regionally. Distribution is related to the history of various population groups.

Quebec is no exception. In fact, 6,000 French Canadian settlers from Quebec City and its surroundings settled in the Lower St. Lawrence region about the end of the 17th and beginning of the 18th centuries. The fact that most present day inhabitants of the Lower St. Lawrence region descend from this small group of settlers suggests a genetic founder effects. Indeed, certain founder mutations are transmitted to a large number of descendants, which increases the risk of genetic diseases in offspring.

As a matter of fact, Dr. Michaud's team identified three C5ORF42 mutations that are common to most of the families in the study. In all, seven families that are carriers of the gene were identified in a 400-km area along Route 132.

In the space of about two centuries, the first colonists settled in the Lower St. Lawrence region and from there other families headed out to settle along the river heading east as far as Mont-Joli and then along the Matapedia River. According to Myriam Srour, a doctoral student and co-author of the study, the mutations likely spread in the population along these migration routes.

So far 15 genes that play a role in the expression of the syndrome have been revealed elsewhere in the world. Dr. Michaud and his team will continue their research to better understand the exact function of the gene and the specific effect of each mutation.

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Gene that causes Joubert Syndrome discovered

ScienceDaily (May 9, 2012) For the first time, scientists at Fred Hutchinson Cancer Research Center have transplanted brain cancer patients' own gene-modified blood stem cells in order to protect their bone marrow against the toxic side effects of chemotherapy. Initial results of the ongoing, small clinical trial of three patients with glioblastoma showed that two patients survived longer than predicted if they had not been given the transplants, and a third patient remains alive with no disease progression almost three years after treatment.

"We found that patients were able to tolerate the chemotherapy better and without negative side effects after transplantation of the gene-modified stem cells than patients in previous studies who received the same type of chemotherapy without a transplant of gene-modified stem cells," said Hans-Peter Kiem, M.D., senior and corresponding author of the study published in the May 9 issue of Science Translational Medicine.

Kiem, a member of the Clinical Research Division at the Hutchinson Center, said that a major barrier to effective use of chemotherapy to treat cancers like glioblastoma has been the toxicity of chemotherapy drugs to other organs, primarily bone marrow. This results in decreased blood cell counts, increased susceptibility to infections and other side effects. Discontinuing or delaying treatment or reducing the chemotherapy dose is generally required, but that often results in less effective treatment.

In the current study, Kiem and colleagues focused on patients with glioblastoma, an invariably fatal cancer. Many of these patients have a gene called MGMT (O6-methylguanine-DNA-methyltransferase) that is turned on because the promoter for this gene is unmethylated. MGMT is a DNA repair enzyme that counteracts the toxic effect of some chemotherapy agents like temozolomide. Patients with such an unmethylated promoter status have a particularly poor prognosis.

A drug called benzylguanine can block the MGMT gene and make tumor cells sensitive to chemotherapy again, but when given with chemotherapy, the toxic effects of this combination are too much for bone marrow cells, which results in marrow suppression.

By giving bone marrow stem cells P140K, which is a modified version of MGMT, those cells are protected from the toxic effects of benzylguanine and chemotherapy, while the tumor cells are still sensitive to chemotherapy. "P140K can repair the damage caused by chemotherapy and is impervious to the effects of benzylguanine," Kiem said.

"This therapy is analogous to firing at both tumor cells and bone marrow cells, but giving the bone marrow cells protective shields while the tumor cells are unshielded," said Jennifer Adair, Ph.D., who shares first authorship of the study with Brian Beard, Ph.D., both members of Kiem's lab.

The three patients in this study survived an average of 22 months after receiving transplants of their own circulating blood stem cells. One, an Alaskan man, remains alive 34 months after treatment. Median survival for patients with this type of high-risk glioblastoma without a transplant is just over a year.

"Glioblastoma remains one of the most devastating cancers with a median survival of only 12 to 15 months for patients with unmethylated MGMT," said Maciej Mrugala, M.D., the lead neuro oncologist for this study.

As many as 50 percent to 60 percent of glioblastoma patients harbor such chemotherapy-resistant tumors, which makes gene-modified stem cell transplant therapy applicable to a large number of these patients. In addition, there are also other brain tumors such as neuroblastoma or other solid tumors with MGMT-mediated chemo resistance that might benefit from this approach.

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Gene-modified stem cell transplant protects patients from toxic side effects of chemotherapy, study suggests