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April 17, 2014

Modified Stem Cells May Offer Way to Treat Alzheimer’s Disease

(Medical News Today) – A new study suggests genetically modified stem cells may offer a new way to treat Alzheimer’s disease. When implanted in mice bred to have symptoms and brain hallmarks of Alzheimer’s, they increased connections between brain cells and reduced the amyloid-beta protein that accumulates to form plaques that clog up the brain.

Fertility Mystery Solved: Protein Discovered that Joins Sperm with Eggs

(The Guardian) – A fundamental key to fertility has been uncovered by British scientists with the discovery of an elusive protein that allows eggs and sperm to join together. The molecule – named Juno after the Roman goddess of fertility – sits on the egg surface and binds with a male partner on a fertilising sperm cell. Japanese researchers identified the sperm protein in 2005, sparking a decade-long hunt for its “mate”.

April 16, 2014

China Bans Genetic Testing

(Genetic Engineering & Biotechnology News) – For nearly a half-century, interrupted only by the Cultural Revolution, China promoted the growth of genetic testing to prevent and address birth defects through state-run hospitals, as well as charities and increasingly in recent years, private enterprises. Then in February, China reversed course. The China Food and Drug Administration posted a new regulation that immediately banned genetic testing—even previously approved services “including prenatal genetic testing, gene sequencing technology-related products, and cutting-edge products and technologies.”

April 15, 2014

Genetic Risk of Alzheimer’s Has Gender Bias

(New Scientist) – Carrying a copy of the “Alzheimer’s gene” doesn’t significantly raise a man’s risk of developing the disease. The gene does increase a woman’s risk, but women with one copy of the gene were as likely to develop the disease as men with no copies. The study – along with work suggesting that the gene is associated with educational achievement in young people – highlights how much remains to be done to untangle the genetics of Alzheimer’s.

Genetics Leader Reflects on 50th Anniversary of Discovery of Genetic Code

(Baylor College of Medicine) – In 1959, postdoctoral associate Dr. Thomas Caskey, participated in the Nobel Prize winning work of Dr. Marshall Nirenberg that helped unravel the genetic code of life. It was not just a “one-trick pony,” Caskey reflected. Nirenberg won the Nobel Prize for this work which unveiled the set of rules by which information encoded without genetic material  (DNA or mRNA sequences) is translated into proteins by living cells.

April 14, 2014

Gene Editing Technology

What Is Gene Editing?

People sometimes express concerns over gene therapy, which is genetic engineering for therapeutic purposes, but what they are really concerned about is gene editing. Genetic engineering is a relatively straightforward procedure in the laboratory, and is the basis of the field of synthetic biology. Genes are made of DNA, and scientists are able to make any DNA sequence they want using a computer and laboratory equipment. Technically speaking, this is genetic engineering. While making a DNA sequence in a lab is relatively simple, inserting it into a cell and replacing the unwanted DNA, is an entirely different technique. The insertion or deletion of DNA may be more accurately described as gene editing.

Gene editing has been notoriously difficult to do. The best techniques have involved designing proteins that take a long time to make and are difficult to work with in the lab. Additionally, these gene editing techniques can only edit one segment of DNA at a time. This makes it difficult for scientists to study disease models (usually in mice) involving more than one genetic marker. Recently, however, several studies have touted a new gene editing technique called CRISPR (clustered regularly interspaced short palindromic repeats) that has already shown in animal models that it is easier to use and can change more than one portion of DNA at a time.

Gene therapy received a bad reputation in 1999 when 18-year-old Jesse Gelsinger, a clinical trial participant, died from a poor reaction to a technique involving the insertion of genetic material to potentially cure a rare genetic disease. This case was controversial for many reasons, including financial conflict-of-interest issues and proper informed consent. As a result of this case, as well as other cases that came to light upon investigation, gene therapy research and clinical trials decreased dramatically for a number of years.  However, a recent Wired article entitled “The Fall and Rise of Gene Therapy” optimistically reported that improvements in gene insertion into cells have led to a resurgence of the field.

(It is notable that the Wired article was criticized for leaving out pertinent historical facts regarding the Gelsinger case and the ethical controversies surrounding the gene therapy field at the time.  An informative response to the article can be found here.

Finding the right virus to target cells and insert DNA segments into those cells is only part of the story.

New Tools for Gene Editing

In order for scientists to determine what a gene actually does and whether it is the cause of a disease, they will do animal studies in which they remove the gene and see what changes occur in the animal, such as looking for disease symptoms. This is usually done in mouse models, and it usually takes many years to adequately remove or “silence” a gene. Using the CRISPR method scientists are now able to remove a gene in a matter of weeks. Additionally, with these techniques they are able to guide where the DNA is inserted, rather than just inserting it randomly into the cell.

Prior methods to delete and insert DNA were more cumbersome. In 1996, scientists developed a technique called zinc-finger nuclease (ZFN) in which scientists made a protein nuclease in the lab that targeted a specific portion of DNA that would then cut the DNA. But, scientists needed to make a new nuclease every time they wanted to investigate a different portion of DNA. This process was expensive and time consuming. It also was only good for one genetic modification at a time, making it difficult to investigate diseases that have more than one genetic marker.

In 2010, scientists developed a different nuclease technique that was easier to work with than ZFNs called TALEN (transcription activator-like effector nucleases). These nucleases are easier to design for a specific DNA target, but their large size presented practical problems in the lab.

Finally, in January 2013, scientists demonstrated that a method that bacteria use to inoculate themselves from viruses can also be used as a gene editing technique in humans. (See here for the research article.) This latest method is CRISPR. It requires a nuclease called CAS9 and a piece of RNA (similar to DNA) that scientists can make in the lab. Unlike prior methods for gene editing, the same nuclease can be used to edit any DNA target. The RNA segment tells the CRISPR/CAS9 system where to cut the DNA. Not only can it remove DNA, but it can also guide the cell’s DNA repair mechanisms to the precise location for inserting the edited DNA. ZFNs and TALENs also use the cell’s repair mechanisms to guide DNA, but CRISPR is much easier to work with and, importantly, much faster. Using CRISPR, several genes can be deleted and others inserted in mouse models in a matter of weeks rather than years. Several research groups and start-up companies are now studying CRISPR and refining the technique.

Use in Stem Cell Therapy

One way that scientists are hoping to use CRISPR is in stem cell therapy. For example, Susan Young in MIT Technology Review reports that Gang Boa’s group is looking into ways to overcome the immune response when a patient receives a donor’s stem cells. They are testing whether they can remove bone marrow stem cells from people with sickle cell disease, use CRISPR to edit out the offending gene sequence that causes sickle cell, and then re-insert the edited stem cells back into the patient. This is just one of several possibilities using CRISPR techniques. According to Young, “In little more than a year, CRISPR has begun reinventing genetic research.”

Bioethics Issues

Many of the same concerns that have been mentioned on this site in regards to genetic engineering apply to gene therapy using CRISPR (See “Mighty Mitochondria and Assisted Reproductive Technology” and “Genetics in the News”. Not every trait or disease has a purely genetic basis. Also, if someone has a gene for a particular disease, in many cases, that only means he or she may get the disease. Pre-emptively removing a gene that has not been fully characterized may lead to unforeseen adverse effects. Sometimes genes have both “good” and “bad” effects. Additionally, sometimes the same gene may be recruited for different purposes. We, therefore, need to exercise caution when moving into areas in which our knowledge is still incomplete.

The most pressing bioethics issue is that of safety. CRISPR will not be in the clinic for a long time because, just as with its predecessors, ZFNs and TALENS, it sometimes cuts the DNA in the wrong spot.  Off-target cutting can be lethal to cells. Much of the current research on CRISPR is finding ways to ensure accurate editing. Even being off by one nucleotide can wreak havoc on an organism, so until gene editing becomes more accurate, it will continue to be limited to studying model diseases or possibly for stem cell research.

Another ethical issued is raised by Harvard scientist George Church in Young’s MIT Technology Review article. He points out that once gene editing is able to cure diseases, “some scientists will be tempted to use it to engineer embryos during in vitro fertilization. Researchers have already shown that genome editing can rewrite DNA sequences in rat and mouse embryos, and in late January, researchers in China reported that they had created genetically modified monkeys using CRISPR. With such techniques, a person’s genome might be edited before birth—or, if changes were made to the eggs or sperm-­producing cells of a prospective parent, even before conception.”

This brings up issues of autonomy and human dignity. Gene editing techniques could/might allow parents to make genetic decisions for their children. Furthermore, as we have seen with the American eugenics movement, fear of mental illness or other culturally driven preferences may lead some parents to decide to have their embryo’s genome edited without fully understanding the complex genetic basis, if there is a genetic basis, behind these traits. This delves into even more fundamental questions on the role that genetics plays in determining our traits.

The human genome is complex, and scientists are still learning the nuances of the genetic code and how genes are expressed. While using CRISPR technology to study disease in animal models seems to have a practical value, the consequences of editing certain genes in the human genome are still largely unknown. There are a small number of genetic diseases that are directly due to a particular error in the genetic code, but many diseases are due to a complexity of factors in which it’s unclear whether genetic editing would do more harm than good.

For an academic review article on ZFNs, TALENs, and CRISPR, see Trends in Biotechnology, Volume 31, Issue 7, 397-405, 09 May 2013. Subscription required.

Finding the Switch: Researchers Create Roadmap for Gene Expression

(Medical Xpress) – In a new study, researchers from North Carolina State University, UNC-Chapel Hill and other institutions have taken the first steps toward creating a roadmap that may help scientists narrow down the genetic cause of numerous diseases. Their work also sheds new light on how heredity and environment can affect gene expression.

Pure Samples of Individual Amino Acids Successfully Identified through Recognizing Tunneling

(A to Z Nanotechnology) – Some three billion base pairs make up the human genome – the floorplan of life. In 2003, the Human Genome Project announced the successful decryption of this code, a tour de force that continues to supply a stream of insights relevant to human health and disease. Nevertheless, the primary actors in virtually all life processes are the proteins coded for by DNA sequences known as genes.

Brain Cell Discovery Could Open Doors to Targeted Cancer Therapies

(Eurekalert) – Fresh insights into the processes that control brain cell production could pave the way for treatments for brain cancer and other brain-related disorders. Scientists have gained new understanding of the role played by a key molecule that controls how and when nerve and brain cells are formed – a process that allows the brain to develop and keeps it healthy. Their findings could help explain what happens when cell production goes out of control, which is a fundamental characteristic of many diseases including cancer.

April 11, 2014

A New Edition of Developing World Bioethics is Available

Developing World Bioethics (Volume 14, No. 1, April 2014) is now available online by subscription only.

Articles include:

  • “Bioethics and Forensic Psychiatry” by Debora Diniz
  • “Impact of Three Years Training on Operations Capacities of Research Ethics Committees in Nigeria” by Morenike Oluwatoyin Folayan, et al.
  • “On Abortion: Exploring Psychological Meaning and Attitudes in a Sample of Mexican Gynecologists” by Ma. Luisa Marván, Asunción Álvarez del Río and Zaira Campos
  • “Ethical Issues in Field Trials of Genetically Modified Disease-Resistant Mosquitoes” by David B. Resnik
  • “The Ethics of Engaged Presence: A Framework for Health Professionals in Humanitarian Assistance and Development Work” by Matthew R. Hunt, et al.

A New Edition of Journal of Medical Ethics is Available

Journal of Medical Ethics (Volume 40, No. 4, April 2014) is now available online by subscription only.

Articles include:

  • “Freedom and moral enhancement” by Michael J Selgelid
  • “The duty to be Well-informed: The case of depression” by Charlotte Blease
  • “Approaches to suffering at the end of life: the use of sedation in the USA and Netherlands” by Judith AC Rietjens, et al.
  • “Moral concerns with sedation at the end of life” by Charles Douglas
  • “Genetic modifications for personal enhancement: a defence” by Timothy F Murphy
  • “Voluntary moral enhancement and the survival-at-any-cost bias” by  Vojin Rakić
  • “Embryonic viability, parental care and the pro-life thesis: a defence of Bovens” by Jonathan Surovell
  • “Differentiating between human and non-human interspecies embryos” by Calum MacKellar

Researchers Identify Transcription Factors Distinguishing Glioblastoma Stem Cells

(Medical Xpress) – The activity of four transcription factors – proteins that regulate the expression of other genes – appears to distinguish the small proportion of glioblastoma cells responsible for the aggressiveness and treatment resistance of the deadly brain tumor. The findings by a team of Massachusetts General Hospital (MGH) investigators, which will be published in the April 24 issue of Cell and are receiving advance online release, support the importance of epigenetics – processes controlling whether or not genes are expressed – in cancer pathology and identify molecular circuits that may be targeted by new therapeutic approaches.

April 10, 2014

Copper Can Block Growth of Rare Cancer

(The Telegraph) – A need for copper could be the Achilles’ heel of some cancers, scientists believe. It may allow them to be tackled with drugs used to block copper absorption in patients suffering from a rare disease. Cancers with a mutation in the BRAF gene need copper to promote their growth, according to research published in the journal Nature. They include melanoma, the most dangerous form of skin cancer that kills more than 2,000 people in Britain each year.

April 9, 2014

Fearing Punishment for Bad Genes

(New York Times) – About 700,000 Americans have had their DNA sequenced, in full or in part, and the number is rising rapidly as costs plummet — to $1,000 or less for a full genome, down from more than $1 million less than a decade ago. But many people are avoiding the tests because of a major omission in the 2008 federal law that bars employers and health insurers from seeking the results of genetic testing.

Could Gene Therapy Switch Off Paralysis?

(The Epoch Times) – Researchers have identified a coding gene that has a profound effect on the central nervous system. They say the finding could shed light on paralysis, stroke, and other disorders of the central nervous system, including Alzheimer’s disease. Coding genes contain DNA sequences that are used to assign functions required for development and maintenance within a cell. These coding genes articulate how a fingernail grows, help develop nerve cells responsible for chewing, and are vital in helping the spinal cord facilitate movement in arms or legs.

April 8, 2014

DNA Nanobots Deliver Drugs in Living Cockroaches

(New Scientist) – It’s a computer – inside a cockroach. Nano-sized entities made of DNA that are able to perform the same kind of logic operations as a silicon-based computer have been introduced into a living animal. The DNA computers – known as origami robots because they work by folding and unfolding strands of DNA – travel around the insect’s body and interact with each other, as well as the insect’s cells. When they uncurl, they can dispense drugs carried in their folds.

April 7, 2014

Friedreich’s Ataxia: An Effective Gene Therapy in an Animal Model

(Medical Xpress) – The team led by Hélène Puccio, director of research for Inserm at the Institute of Genetics and Molecular and Cellular Biology in close collaboration with Patrick Aubourg’s team has demonstrated, in the mice, the efficacy of gene therapy for treating the heart disease associated with Friedreich’s ataxia, a rare hereditary neuro-degenerative disorder. The transfer, via a viral vector, of a normal copy of the gene deficient in patients, allowed to fully and very rapidly cure the heart disease in mice. These findings are published in Nature Medicine on 6 April, 2014.

Amino Acid Fingerprints Revealed in New Study

(Phys.org) – Now, Stuart Lindsay and his colleagues at Arizona State University’s Biodesign Institute have taken a major step in this direction, demonstrating the accurate identification of amino acids, by briefly pinning each in a narrow junction between a pair of flanking electrodes and measuring a characteristic chain of current spikes passing through successive amino acid molecules.

Genetic Testing to Predict Menopause

(The Sydney Morning Herald) – A genetic test to predict the start of menopause is likely to be available within five years, allowing women to make more informed decisions about their health and fertility, a leading expert says. Professor of Reproductive Medicine and Gynaecology at University Medical Centre in the Netherlands, Bart Fauser, said given menopause could begin at very different ages, including before 40 years for about one in 100 women, a test to more precisely predict the timing would be extremely useful, especially for women wanting children.

April 3, 2014

Pharmocogenomics Has Not Fulfilled Its Promise to Developing Countries

(Science Daily) – From 1997 to 2010, despite promises made by the international scientific community, pharmacogenomic research produced few studies focusing on rare, orphan and tropical diseases prevalent in developing countries. Catherine Olivier, bioethics research at the University of Montreal’s School of Public Health, recently published these findings in the journal Global Public Health.

Gene Therapy Improves Limb Function Following Spinal Cord Injury

(Medical Xpress) – Delivering a single injection of a scar-busting gene therapy to the spinal cord of rats following injury promotes the survival of nerve cells and improves hind limb function within weeks, according to a study published April 2 in The Journal of Neuroscience. The findings suggest that, with more confirming research in animals and humans, gene therapy may hold the potential to one day treat people with spinal cord injuries.

 

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