Archive for the ‘Gene Therapy Research’ Category
Want to Live a Long Time? Pay Attention
Long before the age of gene therapy and miracle medical treatments, the secrets of long life were being gathered and revealed in a unique study of 1,500 children born about 1910. By studying these people throughout their lives, successive generations of researchers collected nearly 10 million pieces of observable data and have been able to produce solid insights into human longevity.
"Most people who live to an old age do so not because they have beaten cancer, heart disease, diabetes, or lung disease; rather, the long-lived have mostly avoided serious ailments altogether," Howard S. Friedman and Leslie R. Martin said in their 2011 book, "The Longevity Project."
"The best childhood personality predictor of longevity was conscientiousness--the qualities of a prudent, persistent, well-organized person," according to the two professors (he at the University of California--Riverside, and she at La Sierra University). "Conscientiousness ... also turned out to be the best personality predictor of long life when measured in adulthood."
[Read: Do You Recognize These Lessons of Longevity?]
Since their book was published, Martin recently told U.S. News, the benefits of conscientiousness have been affirmed and even strengthened in other research studies. "This is still a pretty hot topic," she says. "Work that's come out since the book was published has mainly confirmed the importance of conscientiousness."
In particular, she explained, research being done in Hawaii on personality traits over time is producing similar results to Friedman's and Martin's own research, which chronicles efforts begun in 1921 by Lewis Terman, a Stanford University psychologist. He selected 1,500 bright and generally high-performing children and began amassing detailed information about their personal histories, health, activities, beliefs, attitudes, families and other variables.
Over the next eight decades, other academics maintained the Terman Project and assembled exhaustive details on all facets of the original subjects' later lives. It is this unique depth of detail that has permitted Friedman and Martin to reach what they feel are scientifically sound conclusions about what it takes to live a long life. Now, Martin says, more researchers are reaching similar conclusions.
"It was not cheerfulness and it was not having a sociable personality that predicted long life across the many ensuing decades," she and Friedman wrote in their book. "Certain other factors were also relevant, but the prudent, dependable children lived the longest. The strength of this finding was unexpected, but it proved to be a very important and enduring one."
The book presents three reasons why conscientious people live longer:
1. They are more likely to obey the rules, protecting their health and not engaging in risky behaviors such as smoking or driving without a seat belt. If a doctor tells them to take a medicine, they take every prescribed dose.
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Want to Live a Long Time? Pay Attention
Gene linked to nearly twice Alzheimer's risk in African-Americans
Apr. 9, 2013 African-Americans with a variant of the ABCA7 gene have almost double the risk of developing late-onset Alzheimer's disease compared with African-Americans who lack the variant. The largest genome-wide search for Alzheimer's genes in the African-American community, the study was undertaken by the Alzheimer's Disease Genetics Consortium and led by neurologists from Columbia University Medical Center.
It will be published in the April 10 issue of the Journal of the American Medical Association. The study was primarily funded by the National Institutes of Health (NIH).
"Our findings strongly suggest that ABCA7 is a definitive genetic risk factor for Alzheimer's disease among African-Americans," said study senior author, Richard Mayeux, MD, MS, professor and chair of Neurology at CUMC. "Until now, data on the genetics of Alzheimer's in this patient population have been extremely limited."
The ABCA7 gene is involved in the production of cholesterol and lipids, which suggests that lipid metabolism may be a more important pathway in Alzheimer's disease in African-Americans than in whites. Because cholesterol and lipid imbalances (which eventually lead to vascular disease and heart attacks and strokes) are more common in African-Americans, treatments that reduce cholesterol and vascular disease may potentially be an effective way to reduce or delay Alzheimer's in this population.
"While we need to conduct research to determine whether reducing cholesterol will lower the chance of Alzheimer's in African-Americans, maintaining healthy cholesterol levels always has the benefit of lowering one's risk of heart attack and stroke," said Dr. Mayeux.
The study involved nearly 6,000 African-American participants, most of whom are volunteers from 18 NIH-funded Alzheimer's Disease Centers. The Centers and other researchers contributed samples to the Alzheimer's Disease Genetics Consortium, an NIH-supported research program led by Gerard D. Schellenberg, PhD, at the University of Pennsylvania. Approximately 2,000 of the volunteers were diagnosed with probable Alzheimer's disease and 4,000 were cognitively normal. The purpose of the study was to look for genetic variants among African-Americans, who are known to have a higher incidence of late-onset Alzheimer's than whites living in the same community. Ninety percent of all cases of Alzheimer's, which affect an estimated 5 million Americans aged 65 and older, are described as having the late-onset form of the disease.
"ABCA7 is the first major gene implicated in late-onset Alzheimer's among African Americans, and it has an effect on disease risk comparable to that of APOE-e4 -- which has been known for two decades to be a major genetic risk factor in whites," said Christiane Reitz, MD, PhD, assistant professor of neurology, who conducted the study's genetic analyses as first author on the paper. "Both genes raise the risk of Alzheimer's in this population twofold." The extent of the role of APOE-e4 in African-Americans had been uncertain because of inconsistent results from previous, smaller studies.
"Based on these results, we now know that both APOE-e4 and ABCA7 are major genetic risk factors for African-Americans, whereas for whites, only one of the two -- APOE-e4 -- confers a similar degree of risk," said Dr. Mayeux, who is also co-director of the Taub Institute for Research on Alzheimer's Disease and the Aging Brain and the Gertrude H. Sergievsky Center at CUMC. He is the Gertrude H. Sergievsky Professor of Neurology, Psychiatry and Epidemiology.
Several other genes that had recently been linked to Alzheimer's in white populations were also confirmed in the current study to play a role in African-Americans. "Because they cross ethnic groups, the likelihood increases that these genes are very important in the development of Alzheimer's," said Dr. Reitz, who is a member of both the Sergievsky Center and the Taub Institute. "And that gives us clues in our search for the cellular pathways associated with the disease."
"These findings suggest that the genetic underpinnings of Alzheimer's disease may vary among different populations -- and so should not be treated homogeneously," said Dr. Reitz.
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Gene linked to nearly twice Alzheimer's risk in African-Americans
Alzheimer's Gene Doubles Risk In African-Americans
Editor's Choice Academic Journal Main Category: Alzheimer's / Dementia Also Included In: Genetics Article Date: 10 Apr 2013 - 11:00 PDT
Current ratings for: Alzheimer's Gene Doubles Risk In African-Americans
The research, the largest analysis yet to establish genetic risk linked to late-onset Azheimer's disease in African-Americans, was undertaken by the Alzheimer's Disease Genetics Consortium and led by scientists from Columbia University Medical Center.
"Our findings strongly suggest that ABCA7 is a definitive genetic risk factor for Alzheimer's disease among African-Americans," said Richard Mayeux, MD, MS, professor and chair of Neurology at CUMC. "Until now, data on the genetics of Alzheimer's in this patient population have been extremely limited."
The ABCA7 gene plays a part in the production of lipids and cholesterol, which indicates that lipid metabolism might be a more crucial pathway for the disease in African-American individuals than in whites.
It is more common for African-Americans to experience lipid and cholesterol imbalances - which ultimately result in heart attacks, strokes, and vascular disease. Therefore, the authors explained that treatments that lower cholesterol and vascular disease could possibly be a successful way to decrease or delay Alzheimer's among this group of people.
"While we need to conduct research to determine whether reducing cholesterol will lower the chance of Alzheimer's in African-Americans, maintaining healthy cholesterol levels always has the benefit of lowering one's risk of heart attack and stroke," said Dr. Mayeux.
The experts aimed to look for genetic variants in African-Americans, who generally have an increased incidence of late-onset Alzheimer's, compared to whites residing in the same community. Alzheimer's affects approximately 5 million people aged 65 and older in the U.S., and 90% of all cases of the disease are reported to be the late-onset form.
Christiane Reitz, MD, PhD, first author and assistant professor of neurology, said:
The importance of the role of APOE-e4 in African-Americans had been unclear due to conflicting results from prior, smaller investigations.
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Alzheimer's Gene Doubles Risk In African-Americans
Gene May Double Risk of Alzheimer's in Blacks
By Amy Norton HealthDay Reporter
TUESDAY, April 9 (HealthDay News) -- A particular variant of a cholesterol-related gene may double the risk of Alzheimer's disease in older blacks, a new study suggests.
The gene -- known as ABCA7 -- is also linked to Alzheimer's among whites, but it appears much more important in blacks' risk of the memory-robbing disease, the researchers said.
Still, although a doubling in risk may sound large, the researchers stressed that it's actually a modest increase. Older adults' risk of Alzheimer's is thought to depend on many factors -- not only an array of different genes, but also environmental influences.
"How much does this increase your risk? It's modest," said Dr. Robert Nussbaum, a professor of medicine at the University of California, San Francisco, who was not involved in the study.
But the findings are important because they add to the understanding of the complex underpinnings of Alzheimer's, said Nussbaum, who wrote an editorial published with the study in the April 10 issue of the Journal of the American Medical Association.
The results come from what is believed to be the most extensive search yet for Alzheimer's-linked genes in older blacks.
Most of what is known about Alzheimer's genes has come from data on white adults, because until now there hadn't been a study sample of blacks that was large enough for a gene study, said study lead researcher Dr. Christiane Reitz, an assistant professor of neurology at Columbia University Medical Center in New York City.
Researchers have known for years that whites with a particular variant in the ApoE gene -- called ApoE4 -- have a higher risk of Alzheimer's than whites who carry other variants of the gene.
About 25 percent to 30 percent of the population is thought to carry the Alzheimer's-linked E4 variant.
MediPoint: Predictive Breast Cancer Gene Testing – EU Analysis and Market Forecasts
NEW YORK, April 11, 2013 /PRNewswire/ -- Reportlinker.com announces that a new market research report is available in its catalogue:
MediPoint: Predictive Breast Cancer Gene Testing - EU Analysis and Market Forecasts http://www.reportlinker.com/p01158474/MediPoint-Predictive-Breast-Cancer-Gene-Testing---EU-Analysis-and-Market-Forecasts.html#utm_source=prnewswire&utm_medium=pr&utm_campaign=Pathology
MediPoint: Predictive Breast Cancer Gene Testing - EU Analysis and Market Forecasts
Summary
Breast cancer is the most common form of cancer in women in both the developed and developing world. The incidence of breast cancer is increasing due to the increased life span and increasing adoption of Western lifestyle risk factors. Predictive breast cancer gene tests can be used to identify women who are at increased risk of developing hereditary breast cancer. The Predictive Breast Cancer Gene Testing market has seen exponential growth in the US, dominated by Myriad Genetics. Gene testing in Europe is mostly carried out by the state funded health sector, but increasingly private companies are offering breast cancer gene tests to physicians. Myriad Genetics' position in the market is dependent on it being the leading provider of the most common breast cancer mutations. By the end of our forecast period, the competitive landscape will experience significant change due to the erosion of Myriad Genetics' position, as a result of the expiry of key patents, and the emergence of alternative molecular technologies.
This report focuses on the predictive breast cancer gene testing markets in Europe (France, Germany, Italy, Spain, and the UK), and identifies unmet needs in the market, physician attitudes towards current gene testing, and the future of gene testing in the face of rapid technological advancement.
Scope
- An overview of Breast Cancer, which includes epidemiology, etiology, symptoms, diagnosis, pathology and treatment guidelines. - Annualized EU Breast Cancer Gene Testing market revenue and future forecasts from 2009 to 2011, forecast for 7 years to 2018. - Investigation of current and future market competition for Breast Cancer Gene Testing - Insightful review of the key industry drivers, restraints and challenges as well as predicted impact of key events. - Competitor assessment including device approval analysis and device sales forecasts. - Marketed and pipeline product profiles covering efficiency, safety, clinical study details, device approvals, product positioning and device sales forecast. - Analysis of unmet needs within the market and opportunities for future players. - Technology trends evaluation to assess strength of pipeline. - An overview of all devices in development including clinical study details, design and material selection considerations, efficacy reports, and device approval timelines. - Company profiles including business description, financial overview and SWOT analysis. - Coverage of key market players. - Strategic assessment of EU device sector through market impact analysis, future market scenario and company analysis. - Direct quotes from Key Opinion Leaders (KOL) as well as oncologists
Reasons to buy
- Understand the trends shaping and driving EU Breast Cancer Gene Testing Market. - Realize device preferences of physicians who have performed the tests already. - Access market sizing, forecasts and quantified growth opportunities in EU Breast Cancer Gene Testing Market through 2018. - Quantify candidate patient populations to better design product pricing & launch plans. - Drive revenues, formulate effective sales and marketing strategies and gain in-depth understanding of the competitive landscape. - Perform benchmarking analysis of growth opportunities against currently marketed products. - Assess competitiveness of products in market by understanding the strengths and weaknesses of current competition. - Take a comprehensive look at the market's device pipeline and identify promising, paradigm-shifting products. - Create an effective counter-strategy to gain a competitive advantage against those currently in the market. - Organize your sales and marketing efforts by identifying the market categories and segments that present the best opportunities for growth. - What's the next big thing in EU Breast Cancer Gene Testing market landscape? Identify, understand and capitalize.
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MediPoint: Predictive Breast Cancer Gene Testing - EU Analysis and Market Forecasts
MediPoint: Predictive Breast Cancer Gene Testing – US Analysis and Market Forecasts
NEW YORK, April 11, 2013 /PRNewswire/ -- Reportlinker.com announces that a new market research report is available in its catalogue:
MediPoint: Predictive Breast Cancer Gene Testing - US Analysis and Market Forecasts http://www.reportlinker.com/p01158473/MediPoint-Predictive-Breast-Cancer-Gene-Testing---US-Analysis-and-Market-Forecasts.html#utm_source=prnewswire&utm_medium=pr&utm_campaign=Pathology
MediPoint: Predictive Breast Cancer Gene Testing - US Analysis and Market Forecasts
Summary
Breast cancer is the most common form of cancer in women in both the developed and developing world. The incidence of breast cancer is increasing due to the increased life span and increasing adoption of Western lifestyle risk factors. Predictive breast cancer gene tests can be used to identify women who are at increased risk of developing hereditary breast cancer. The Predictive Breast Cancer Gene Testing market has seen exponential growth in the US, dominated by Myriad Genetics. Gene testing in Europe is mostly carried out by the state funded health sector, but increasingly private companies are offering breast cancer gene tests to physicians. Myriad Genetics' position in the market is dependent on it being the leading provider of the most common breast cancer mutations. By the end of our forecast period, the competitive landscape will experience significant change due to the erosion of Myriad Genetics' position, as a result of the expiry of key patents, and the emergence of alternative molecular technologies.
This report focuses on the predictive breast cancer gene testing markets in the US and identifies unmet needs in the market, physician attitudes towards current gene testing, and the future of gene testing in the face of rapid technological advancement.
Scope
- An overview of Breast Cancer, which includes epidemiology, etiology, symptoms, diagnosis, pathology and treatment guidelines. - Annualized US Breast Cancer Gene Testing market revenue and future forecasts from 2009 to 2011, forecast for 7 years to 2018. - Investigation of current and future market competition for Breast Cancer Gene Testing - Insightful review of the key industry drivers, restraints and challenges as well as predicted impact of key events. - Competitor assessment including device approval analysis and device sales forecasts. - Marketed and pipeline product profiles covering efficiency, safety, clinical study details, device approvals, product positioning and device sales forecast. - Analysis of unmet needs within the market and opportunities for future players. - Technology trends evaluation to assess strength of pipeline. - An overview of all devices in development including clinical study details, design and material selection considerations, efficacy reports, and device approval timelines. - Company profiles including business description, financial overview and SWOT analysis. - Coverage of key market players. - Strategic assessment of the US device sector through market impact analysis, future market scenario and company analysis. - Direct quotes from Key Opinion Leaders (KOL) as well as oncologists
Reasons to buy
- Understand the trends shaping and driving the US Breast Cancer Gene Testing Market. - Realize device preferences of physicians who have performed the tests already. - Access market sizing, forecasts and quantified growth opportunities in the US Breast Cancer Gene Testing Market through 2018. - Quantify candidate patient populations to better design product pricing & launch plans. - Drive revenues, formulate effective sales and marketing strategies and gain in-depth understanding of the competitive landscape. - Perform benchmarking analysis of growth opportunities against currently marketed products. - Assess competitiveness of products in market by understanding the strengths and weaknesses of current competition. - Take a comprehensive look at the market's device pipeline and identify promising, paradigm-shifting products. - Create an effective counter-strategy to gain a competitive advantage against those currently in the market. - Organize your sales and marketing efforts by identifying the market categories and segments that present the best opportunities for growth. - What's the next big thing in the US Breast Cancer Gene Testing market landscape? Identify, understand and capitalize.
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MediPoint: Predictive Breast Cancer Gene Testing - US Analysis and Market Forecasts
Syros Pharmaceuticals Announces Publications in Cell Related to Key Gene Control Discovery
WATERTOWN, Mass.--(BUSINESS WIRE)--
Syros Pharmaceuticals, a newly launched company harnessing breakthroughs in gene control to revolutionize the treatment of cancer and other diseases, today announced the publication of new research findings in the journal Cell. The research validates the approach of mapping and targeting newly identified gene control domains, known as Super-Enhancers, for drug discovery and development in cancer and other diseases. The discovery of Super-Enhancers is the basis of Syros' unique platform to identify and modulate pivotal events in disease pathogenesis and critical disease-driver targets.
Syros Co-founder Richard A. Young, Ph.D., who is a Member of the Whitehead Institute, and Professor of Biology at Massachusetts Institute of Technology, led the groundbreaking gene control research. Syros Co-founder James E. (Jay) Bradner, M.D., Assistant Professor of Medicine, Harvard Medical School and Investigator, Department of Medical Oncology, Dana Farber Cancer Institute, co-authored the research, which was funded by the National Institutes of Health and the National Cancer Institute. Syros recently completed a licensing agreement with the Whitehead Institute and the Dana Farber Cancer Institute for intellectual property related to this gene control discovery and other gene control technologies and assets.
Given the complexity of gene expression, the discovery of a small number of powerful gene control regulators provides a promising and exciting new approach to understanding key determinants of cell identity in normal and disease states, said Dr. Young. We have identified Super-Enhancers with key cancer driving genes in all tumors studied and have demonstrated that we can selectively disrupt these genes through inhibition of enhancer factors.
The new research published in back-to-back papers in Cell uncovered that master transcription factors form powerful gene control regulators, called Super-Enhancers, at key cell identity genes; that Super-Enhancers differ from enhancers in their size, transcription factor density and content; that the repertoire of genes that they regulate is unique to each cell type; and that they are important switches for driving cell type specific gene expression programs. In one of the research papers, Super-Enhancers were identified in cancer cells associated with key oncogene drivers and disruption of Super-Enhancers by inhibition of enhancer factors resulted in a preferential inhibition of Super-Enhancer driven genes. The papers, Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers1 and Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes,2 are published in the April 11th print edition of Cell and available online.
This research, which highlights discovery of the master switches for genes critical in disease, gives Syros a completely new approach to identify and modulate disease driver genes, said Nancy Simonian, M.D., Syros Chief Executive Officer. We look forward to translating the pioneering research of Drs. Young and Bradner into therapeutics that can help people facing a variety of diseases, especially cancer.
Syros also announced today the closing of a $30 million Series A financing led by ARCH Venture Partners and Flagship Ventures. Other investors include WuXi PharmaTech Corporate Venture Fund, and undisclosed private investors.
About Syros Pharmaceuticals
Syros Pharmaceuticals is a life sciences company harnessing breakthroughs in gene control to revolutionize the treatment of cancer and other diseases. Syros proprietary platform identifies the master switches for disease genes, opening a whole new approach to novel therapeutics. Syros initial focus is in cancer, but the company platform will also be applicable to other therapeutic areas. The Companys founders are pioneers in gene control research and translation. Co-founded and backed by Flagship Ventures and ARCH Venture Partners, Syros Pharmaceuticals is located in Watertown, MA. For more information, visit http://www.syros.com.
1 Loven, J., Hoke, H., Yin, C., Lau, A., Orlando, D., Vakoc, C., Bradner, J., Lee, T. & Young, R. (2013). Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell, 153(2).
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Syros Pharmaceuticals Announces Publications in Cell Related to Key Gene Control Discovery
Genetic engineering with cabbages – Video
Genetic engineering with cabbages
Ellie, Ari, and cabbages.
By: ELLIEISDEADLY
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Genetic engineering with cabbages - Video
Feed The Beast [Minecraft Modpack] [HD|German] # 1 – Start mit nicem Biom :D – Video
Feed The Beast [Minecraft Modpack] [HD|German] # 1 - Start mit nicem Biom 😀
Kanal: http://www.youtube.com/user/Cezesslp mit dabei: http://www.youtube.com/user/Byntor Minecraft Modpack by Feed the Beast Team: http://www.feed-the-beast...
By: CezessLP
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Feed The Beast [Minecraft Modpack] [HD|German] # 1 - Start mit nicem Biom 😀 - Video
Mast cells have critical role in initializing pulmonary fibrosis
Public release date: 11-Apr-2013 [ | E-mail | Share ]
Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News
New Rochelle, NY, April 11, 2013Pulmonary fibrosis is a chronic, deadly disease that affects five million people worldwide. It is irreversible, its cause is poorly understood, and it has a median survival of only about 3 years. A new study that implicates mast cellsan immune cell involved in allergic asthmain the development of idiopathic pulmonary fibrosis could lead to new, more effective therapies. The study is published in DNA and Cell Biology, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the DNA and Cell Biology website at http://www.liebertpub.com/dna.
In the article "Mast Cells: A Pivotal Role in Pulmonary Fibrosis," A. Veerappan and colleagues from Weill Cornell Medical College, New York, NY, showed that in mice unable to produce mast cells, a chemical trigger known to cause pulmonary fibrosis does not result in disease. However, when the researchers introduced mast cells into the lungs of these mice, disease protection was reversed and the mice developed pulmonary fibrosis. The authors identify a role for two key compounds produced by mast cellshistamine and reninand propose that they promote fibrogenesis when mast cells are activated early in the course of the disease.
Editor-in-Chief Carol Shoshkes Reiss, PhD, Departments of Biology and Neural Science, New York University, NY says, "Randi Silver's lab has shown, in this compelling paper, that mast cells contribute to the pathogenesis of pulmonary fibrosis. These observations are important and may lead to the development of new therapeutic modalities to prevent deterioration of lung function."
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About the Journal
DNA and Cell Biology is the trusted source for authoritative, peer-reviewed reporting on the latest research in the field of molecular biology. By combining mechanistic and clinical studies from multiple systems in a single journal, DNA and Cell Biology facilitates communication among biological sub-disciplines. Coverage includes gene structure, function, and regulation; molecular medicine; cellular organelles; protein biosynthesis and degradation; and cell-autonomous inflammation and host cell response to infection. Complete tables of content and a sample issue may be viewed on the DNA and Cell Biology website at http://www.liebertpub.com/dna.
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 Human Gene Therapy, Antioxidants & Redox Signaling, and AIDS Research and Human Retroviruses. 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 more than 70 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website at http://www.liebertpub.com.
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Mast cells have critical role in initializing pulmonary fibrosis
Nanoparticles boost therapeutic potential of siRNA drugs
Public release date: 10-Apr-2013 [ | E-mail | Share ]
Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 x2156 Mary Ann Liebert, Inc./Genetic Engineering News
New Rochelle, NY, April 10, 2013New classes of drugs that can silence specific genes, such as small interfering RNAs (siRNAs), offer great therapeutic potential. But the specific delivery of siRNAs to target cells to exert their effects remains a significant challenge. A novel nanoparticle-based approach that enables more efficient delivery of siRNA drugs is presented in Nucleic Acid Therapeutics, a peer-reviewed journal from Mary Ann Liebert, Inc. publishers (http://www.liebertpub.com). The article is available on the Nucleic Acid Therapeutics website (http://www.liebertpub.com/nat).
Compared to a commonly used lipid-based transport agent, the cSCK nanoparticles described in this article better protected siRNAs from being degraded in the bloodstream and were associated with greater gene silencing efficiency of siRNA drugs.
The study authors, Yuefei Shen, Huafeng Fang, Ke Zhang, and John-Stephen Taylor, Washington University, St. Louis, MO, and Ritu Shrestha and Karen Wooley, Texas A&M University, College Station, TX, attribute the better gene silencing efficiency achieved with cSCKs with improved cell uptake of the siRNAs. They present their findings in the article "Effective Protection and Transfection of siRNA by Cationic Shell-Crosslinked Knedel-Like Nanoparticles (cSCKs)." (http://online.liebertpub.com/doi/full/10.1089/nat.2012.0390)
"The potential of siRNAs as therapeutic agents is immense, but we still have to develop better and more targeted delivery methods for many diseases," says Executive Editor Fintan Steele, PhD, SomaLogic, Inc., Boulder, CO. "The work of Shen and colleagues demonstrates that nanotechnology approaches are rapidly progressing towards the goal of meeting the challenge of delivery."
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Nucleic Acid Therapeutics is under the editorial leadership of Co-Editors-in-Chief Bruce A. Sullenger, PhD, Duke Translational Research Institute, Duke University Medical Center, Durham, NC, and C.A. Stein, MD, PhD, City of Hope National Medical Center, Duarte, CA; and Executive Editor Fintan Steele, PhD (SomaLogic, Boulder, CO).
About the Journal
Nucleic Acid Therapeutics is an authoritative, peer-reviewed journal published bimonthly in print and online that focuses on cutting-edge basic research, therapeutic applications, and drug development using nucleic acids or related compounds to alter gene expression. Nucleic Acid Therapeutics is the Official Journal of the Oligonucleotide Therapeutics Society (http://www.oligotherapeutics.org). Complete tables of content and a free sample issue may be viewed on the Nucleic Acid Therapeutics website (http://www.liebertpub.com/nat).
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Nanoparticles boost therapeutic potential of siRNA drugs
Life Technologies Launches New Bioinformatics Software Platform Enabling Bio-Design and Gene Synthesis from Next …
CARLSBAD, Calif., April 11, 2013 /PRNewswire/ --Life Technologies Corporation (LIFE) today announced the launch of Vector NTI Express Designer, the latest advancement in its Vector NTI software platform, which offers researchers comprehensive and streamlined custom vector and genetic construct design and synthesis. The desktop software tool is designed for molecular biology, metabolic engineering, genetic engineering, and synthetic biology professionals who want to rationally design, assemble and order synthetic genetic "parts," optimizing genetic components for a broad range of applications.
An extension of the Vector NTI software offerings, Express Designer incorporates an integrated gene synthesis service for rapid sequence submission and order placement, effectively building a bridge from DNA sequence to gene synthesis. Customers can use the Express Designer software tools to design custom DNA parts and submit them directly to Life Technologies' GeneArt portal for synthesis.
"Molecular and synthetic biologists can now move from construct design to synthesis faster than ever before," said Nathan Wood, General Manager and Vice President of Synthetic Biology at Life Technologies. "This launch represents a true game changer in the ease, speed and accuracy with which investigators can design and order DNA customized to their needs, as well as the increased confidence they can have that constructs will perform successfully in their experiments."
Vector NTI Express Designer also provides sequence optimization to fine tune expression levels of cloned genes, enables construction of multiple vectors for compatible and simultaneous function, and generates variants from template DNA parts, devices, and circuits more effectively. In addition to designing and ordering custom components, the software also contains an electronic database or "mini electronic lab notebook" that allows researchers to maintain a searchable record of genetic parts, constructs and experimental results that can be referred to and utilized to optimize constructs and circuits.
"The Vector NTI Express Designer will allow us to tackle difficult design challenges in synthetic biology," said Christopher Voigt, Ph.D., associate professor of Biological Engineering at M.I.T. "The software automates and facilitates the design process with an intuitive graphical-user interface where well-characterized and annotated parts can be drag-and-dropped to create standard devices and advanced circuits." Voigt is a leader in the study of circuit design underlying the development of synthetic organisms, a process that requires constructing synthetic multi-gene pathways.
"The power of the Vector NTI Express Designer database is that it allows us to track and analyze our experimental results so that we avoid duplicating effort and focus on getting to the answer more quickly," said Steve Mayfield, Ph.D., professor in the Division of Biological Sciences at the University of California, San Diego. "We can focus more on what we want our constructs to do and less on how to make them do it." Mayfield is a pioneer in the genetic design of organisms such as algae for biofuel production.
Vector NTI Express Designer is built on a the Vector NTI Sequence Analysis and Bioinformatic Tools platform, and so inherits many of the applications associated with that platform, including: sequence analysis and design, annotation, and illustration; molecular biology data management; open reading frame and restriction enzyme analysis and mapping; primer design; recombinant molecule design, including Gateway and TOPO cloning, GeneArt seamless cloning & high-order assembly and gene synthesis.
Built on the trusted history of high-quality sequence analysis and design tools of Vector NTI Software, Vector NTI Express Designer enables rational bio-design on the most popular computing architectures, including native Mac OSX 10.6+, Windows XP, Windows 7, and Windows 8 operating systems. Its plug-in architecture allows users to have confidence that additional features and functionality can be added to the platform and deliver more value over time while its Automatic Updater ensures that users will be automatically notified of updates and given the option to download new or updated plug-ins to always be running the latest, most complete software package available.
For more information, please visit http://www.lifetechnologies.com/vectornti.
All products referenced are for Research Use Only. Not intended for diagnostic uses.
Microbes Can Mass-Produce Malaria Drug
Thanks to extensive genetic engineering, drugmakers can now brew large vats of the malaria drug artemisinin, stabilizing the world supply.
For the first time, researchers have successfully engineered a strain of bakers yeast capable of spewing out malaria drugs on an industrial scale. The French pharmaceutical giant Sanofi has already begun brewing the microbes and announced plans to generate 70 million doses this year.
The advance is the result of a 10-year odyssey in synthetic biology, the wholesale engineering of an organisms genetic and metabolic system for practical purposes (see Biologys Master Programmers).Amyris, the biotech startup that engineered the yeast strain, is also developing microbes to produce fragrances and other high-value chemicals.
This is the first synthetic biology project that has been scaled up to industrial manufacturing and will have a real impact in the world, says Jack Newman, chief scientific officer at Amyris. There should never been a shortage of artemisinin ever again.
Amyris had already engineered yeast capable of producing artemisinic acid, the precursor to the drug (see Cheaper Malaria Drugs). But the most recent advance, published today in Nature, dramatically improved the yield from 1.6 grams per liter to 25 grams per liter.
The improvement primarily comes from the discovery of three key enzymes in sweet wormwood, the plant that naturally produces artemisinin, which researchers then introduced to yeast.
Artemisinin is the primary ingredient in artemisinin combination therapies, the World Health Organizations preferred malaria treatment. But because the drug is primarily derived from plants, its costs can vary from $350 to $1200 per kilogram of the active ingredient.
The botanical supply is inconsistent for various reasons, including weather and incentives for farmers, says Ponni Subbiah, global program leader for drug development at OneWorld Health, a nonprofit drug development organization that funded the research through a grant from the Gates Foundation.
The synthetic process can run year round and takes about three months, compared to 15 months for plant-based methods. Our aim is to stabilize the supply independent of the plant supply, says Chris Paddon, who leads the artemisinin project at Amyris.
OneWorldHealth has licensed the technology to Sanofi, which has already produced nearly 40 tons of the artemisinic acid. (The acid is then chemically converted into artemisinin.) Sanofi aims to produce 60 tons of the material next year approximately 120 million courses of treatment and has pledged to sell it without profit.
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Microbes Can Mass-Produce Malaria Drug
Medical Association Foundation Fundraising Video – Video
Medical Association Foundation Fundraising Video
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Genetic mutations may predict who will develop chemotherapy side effects
Each cancer patients response to chemotherapy is unique. Some may experience nausea and immune deficiency, while others can experience a more severe adverse condition known as chemotherapy-induced peripheral neuropathy (CIPN) a form of nerve damage that can be so debilitating, it often prompts patients to stop treatment early.
Doctors have had a hard time predicting which patients will ultimately develop CIPN, making it difficult to tailor treatment so that it is most effective for each individual. But now, new research has revealed seemingly benign genetic mutations that may influence who develops this painful side effect.
In a study from the Mayo Clinic Cancer Center, researchers have implicated the genes EPHA5, ARHGEF10 and PRX as playing significant roles in the development of CIPN. This discovery can ultimately help doctors to have a better understanding of CIPN and whether or not their patients should move forward with certain cancer treatments.
Chemotherapy-induced peripheral neuropathy is one of the most important, unmitigated side effects of chemotherapy, lead author Dr. Andreas Beutler, an oncologist at the Mayo Clinic Cancer Center, told FoxNews.com. You have some other side effects that used to be very important such as nausea and immune deficiency but special medications have been developed. With CIPN, it has actually become the most prominent and troubling side effect for many chemotherapy patients, because there is no medication for it.
Peripheral neuropathy is caused by damage to the peripheral nerves, which are furthest away from the brain and spinal cord. When chemotherapy damages these nerves, the condition becomes CIPN. Symptoms vary in type and intensity depending on which peripheral nerves are damaged, but they typically include shooting pain, burning, tingling or electric shock-like pain, loss of feeling, balance issues and muscle weakness. The symptoms can become so severe that patients lose the ability to walk normally and are left with permanent numbness in their extremities.
CIPN affects an estimated 30 to 40 percent of patients, but there is no current way to determine who will experience it or how severe it will be.
Beutler and his colleagues decided to analyze the genetics of cancer patients through exome sequencing - a form of DNA analysis that selectively sequences the parts of the genome responsible for coding functional proteins. Known as the exonic region, this area is estimated to house 85 percent of all disease-causing genetic mutations.
The researchers performed exome sequencing on 20,794 genes from 119 cancer patients. Half of the patients were experiencing CIPN during their chemotherapy trial.
The genome is three billion nucleotides, meaning the whole genome has three billion different positions, Beutler said. Out of those, we assessed 60 million of each patient that are best understood the exome. Thereby, we could get a very good view of the part of the genome that is most important and most relevant to our question.
Exome sequencing of the more than 20,000 genes lead the researchers to EPHA5 a previously implicated gene in hereditary peripheral neuropathy as well as two new genes ARHGEF10 and PRX. Genetic mutation in all three areas was associated with a predisposition to CIPN.
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Genetic mutations may predict who will develop chemotherapy side effects
BUSM researchers identify novel approach to study COPD and treatment efficacy
Public release date: 11-Apr-2013 [ | E-mail | Share ]
Contact: Jenny Eriksen jenny.eriksen@bmc.org 617-638-6841 Boston University Medical Center
(Boston) Researchers from Boston University School of Medicine (BUSM) have pinpointed a genetic signature for chronic obstructive pulmonary disease (COPD) from airway cells harvested utilizing a minimally invasive procedure. The findings provide a novel way to study COPD and could lead to new treatments and ways to monitor patient's response to those treatments. The study is published online in the American Journal of Respiratory and Critical Care Medicine.
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that leads to the loss of lung function primarily caused by cigarette smoking. It causes coughing, wheezing, shortness of breath, chest tightness and other symptoms that make it difficult to breathe. While there are treatments and lifestyle changes that can help people cope with COPD, there currently is no cure and there are no effective therapies to reduce the rate of lung function decline. According to the National Institutes of Health's National Heart, Lung, and Blood Institute (NHLBI), which partially funded the study, COPD is the third leading cause of death in the United States, resulting in approximately 135,000 deaths each year.
"There have been limited molecular studies of COPD given the inaccessibility and invasiveness of obtaining lung tissue," said Katrina Steiling, MD, MSc, assistant professor of medicine at BUSM who served as the study's first author. The researchers hypothesized that while COPD primarily affects the tissue deep within the lung, the effects of COPD might be detectable in relatively accessible tissue throughout the respiratory tract. This echoes previous work they had done that found that cancer found deep in the lung could be detected by cancer-specific patterns of gene expression in the largest airways connected to the windpipe, far from the tumor.
To examine their hypothesis, the research team used airway cells obtained during a bronchoscopy, a procedure that involves putting a small camera into the airway through the nose or mouth. During the procedure, which can be done while a patient is awake under local anesthesia or moderate sedation, a cytology brush is used to gently scrape the sides of airways to collect cells.
They examined 238 samples from current and former smokers that had been collected by Stephen Lam, MD, a collaborator from the University of British Columbia. Eighty seven of the samples were from patients who had been diagnosed with mild to moderate COPD based on their lung function. The other 151 samples represented patients who did not have COPD based on these criteria.
When the researchers compared the airway samples from both groups, they found that 98 genes were expressed at different levels in those diagnosed with COPD compared to those without COPD. In order to determine how similar the airway cell changes were to lung tissue cells, the researchers compared their results with previously published findings on the gene expression changes associated with COPD in lung tissue. The results of the comparison demonstrate that the changes that occur in the airway cell samples in those diagnosed with COPD were similar to the changes in lung tissue cells of individuals with the disease despite the airway cells coming from regions of the lung not thought to be altered by disease.
"Our data shows that there are consistent gene-expression changes that occur in both airway and lung tissue cells in individuals with COPD," said Avrum Spira, MD, MSc, Alexander Graham Bell professor of medicine and chief of the division of computational biomedicine at BUSM who served as one of the senior co-authors of the study.
To investigate the effects of treatment on the COPD-associated gene expression changes, the researchers collaborated with a team led by Maarten van den Berge, MD, PhD, from the University of Groningen Medical Center in the Netherlands that had collected airway cells from COPD patients before and after they started steroid therapy. They found that the expression of some genes that changed due to COPD reversed their expression after treatment and started to look more like the levels seen in current or former smokers without COPD.
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BUSM researchers identify novel approach to study COPD and treatment efficacy
Genetic master controls expose cancers' Achilles' heel
Public release date: 11-Apr-2013 [ | E-mail | Share ]
Contact: Matt Fearer fearer@wi.mit.edu 617-452-4630 Whitehead Institute for Biomedical Research
CAMBRIDGE, Mass. (April 11, 2013) In a surprising finding that helps explain fundamental behaviors of normal and diseased cells, Whitehead Institute scientists have discovered a set of powerful gene regulators dubbed "super-enhancers" that control cell state and identity. Healthy cells employ these super-enhancers to control genes responsible for cellular functions and developmental transitionssuch as that from embryonic stem cell to nerve cellbut cancer cells are able to assemble their own insidious super-enhancers to overproduce harmful oncogenes that lead to aggressive tumors.
"We have been marveling at the complexity of cellular control, with millions of enhancers controlling tens of thousands of genes in the vast array of cells that comprise human beings," says Whitehead Member Richard Young. "So it was a surprise to find that only a few hundred super-enhancers control most key genes that give each cell its special properties and functions, and furthermore, that these special controls are hijacked in cancer and other diseases."
The findings are described in dual papers from Young and collaborators at Dana-Farber Cancer Institute published together in the April 11 edition of the journal Cell.
In the first work, the Young lab establishes a model of gene regulation in normal cells that appears to be dramatically less complex and more solvable than previously thought. To date, a vast body of researchincluding that of the recently described ENCODE (Encyclopedia of DNA Elements) projecthas identified more than one million enhancers or "switches" that control gene expression in mammalian cells. Deciphering the precise function and target gene for each of these switches will be a daunting task, but Young and colleagues have found something of a shortcut to solving the core gene control circuitry. They show that only a few hundred special switchesthat is, super-enhancerscontrol the key genes that actually make each cell different.
"What is fantastic about this concept is its simplicity," notes Denes Hnisz, a Young lab postdoctoral scientist and a co-author of the first Cell paper. "We found that genes that are especially important for each cell are regulated by these specialized enhancers. But we also discovered that the super-enhancers are especially quick to change during development, and thus loss of old super-enhancers and establishment of new ones drives cell identity changes during development."
Young says such changes in cell identity probably begin and end with the super-enhancers, which, though powerful, are also exquisitely sensitive to alterations in their environment. In fact, as differentiation begins, active super-enhancers are decommissioned, leading to changes in gene expression programs that fall under the control of newly established super-enhancers. It's a process that adds remarkable insight to our understanding of how a fertilized egg eventually gives rise to the more than one trillion cells of the human body.
"The discovery of super-enhancers promises to help us solve the regulatory circuitry of all human cells," Young says. That includes cancer cells.
While mapping the locations of super-enhancers along the genome of multiple myeloma (MM) cells, which are especially aggressive blood cancer cells, Young lab scientists found them in areas associated with known cancer-causing genes, including the notorious MYC oncogene. It turns out these MM cells were forming their own super-enhancers to drive dangerous overexpression of their oncogenes. Moreover, this phenomenon was not limited to MM cells, as the researchers identified super-enhancers at key tumor genes in small-cell lung cancer and the brain cancer glioblastoma multiforme.
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Genetic master controls expose cancers' Achilles' heel
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