Faulty DNA Linked To Fatal Heart Condition Removed From Embryo

Scientists have modified human embryos to remove genetic mutations that cause heart failure in otherwise healthy young people in a landmark demonstration of the controversial procedure. It is the first time that human embryos have had their genomes edited outside China, where researchers have performed a handful of small studies to see whether the approach could prevent inherited diseases from being passed on from one generation to the next.

While none of the research so far has created babies from modified embryos, a move that would be illegal in many countries, the work represents a milestone in scientists’ efforts to master the technique and brings the prospect of human clinical trials one step closer. The work focused on an inherited form of heart disease, but scientists believe the same approach could work for other conditions caused by single gene mutations, such as cystic fibrosis and certain kinds of breast cancer.

This embryo gene correction method, if proven safe, can potentially be used to prevent transmission of genetic disease to future generations,” said Paula Amato, a fertility specialist involved in the US-Korean study at Oregon Health and Science University.

The scientists used a powerful gene editing tool called Crispr-Cas9 to fix mutations in embryos made with the sperm of a man who inherited a heart condition known as hypertrophic cardiomyopathy, or HCM. The disease, which leads to a thickening of the heart’s muscular wall, affects one in 500 people and is a common cause of sudden cardiac arrest in young people. Humans have two copies of every gene, but some diseases are caused by a mutation in only one of the copies. For the study, the scientists recruited a man who carried a single mutant copy of a gene called MYBPC3 which causes HCM.

Source: https://www.theguardian.com/

How To Capture Quickly Cancer Markers

A nanoscale product of human cells that was once considered junk is now known to play an important role in intercellular communication and in many disease processes, including cancer metastasis. Researchers at Penn State have developed nanoprobes to rapidly isolate these rare markers, called extracellular vesicles (EVs), for potential development of precision cancer diagnoses and personalized anticancer treatments.

Lipid nanoprobes

Most cells generate and secrete extracellular vesicles,” says Siyang Zheng, associate professor of biomedical engineering and electrical engineering. “But they are difficult for us to study. They are sub-micrometer particles, so we really need an electron microscope to see them. There are many technical challenges in the isolation of nanoscale EVs that we are trying to overcome for point-of-care cancer diagnostics.”

At one time, researchers believed that EVs were little more than garbage bags that were tossed out by cells. More recently, they have come to understand that these tiny fat-enclosed sacks — lipids — contain double-stranded DNA, RNA and proteins that are responsible for communicating between cells and can carry markers for their origin cells, including tumor cells. In the case of cancer, at least one function for EVs is to prepare distant tissue for metastasis.

The team’s initial challenge was to develop a method to isolate and purify EVs in blood samples that contain multiple other components. The use of liquid biopsy, or blood testing, for cancer diagnosis is a recent development that offers benefits over traditional biopsy, which requires removing a tumor or sticking a needle into a tumor to extract cancer cells. For lung cancer or brain cancers, such invasive techniques are difficult, expensive and can be painful.

Noninvasive techniques such as liquid biopsy are preferable for not only detection and discovery, but also for monitoring treatment,” explains Chandra Belani, professor of medicine and deputy director of the Cancer Institute,Penn State College of Medicine, and clinical collaborator on the study.

We invented a system of two micro/nano materials,” adds Zheng. “One is a labeling probe with two lipid tails that spontaneously insert into the lipid surface of the extracellular vesicle. At the other end of the probe we have a biotin molecule that will be recognized by an avidin molecule we have attached to a magnetic bead.”

Source: http://news.psu.edu/

Osteoarthritis: NanoParticles Stop Destruction Of Cartilage

Osteoarthritis is a debilitating condition that affects at least 27 million people in the United States, and at least 12 percent of osteoarthritis cases stem from earlier injuries. Over-the-counter painkillers, such as anti-inflammatory drugs, help reduce pain but do not stop unrelenting cartilage destruction. Consequently, pain related to the condition only gets worse. Now, researchers at Washington University School of Medicine in St. Louis have shown in mice that they can inject nanoparticles into an injured joint and suppress inflammation immediately following an injury, reducing the destruction of cartilage.

osteoarthritisResearchers at Washington University School of Medicine in St. Louis have found that injecting nanoparticles into an injured joint can inhibit the inflammation that contributes to the cartilage damage seen in osteoarthritis. Shown in green is an inflammatory protein in cartilage cells. After nanoparticles are injected, the inflammation is greatly reduced


I see a lot of patients with osteoarthritis, and there’s really no treatment,” said senior author Christine Pham, MD, an associate professor of medicine. “We try to treat their symptoms, but even when we inject steroids into an arthritic joint, the drug only remains for up to a few hours, and then it’s cleared. These nanoparticles remain.

Frequently, an osteoarthritis patient has suffered an earlier injury — a torn meniscus or ACL injury in the knee, a fall, car accident or other trauma. The body naturally responds to such injuries in the joints with robust inflammation. Patients typically take drugs such as acetaminophen and ibuprofen, and as pain gets worse, injections of steroids also can provide pain relief, but their effects are short-lived.

In this study, the nanoparticles were injected shortly after an injury, and within 24 hours, the nanoparticles were at work taming inflammation in the joint. But unlike steroid injections that are quickly cleared, the particles remained in cartilage cells in the joints for weeks.

The nanoparticles used in the study are more than 10 times smaller than a red blood cell, which helps them penetrate deeply into tissues. The particles carry a peptide derived from a natural protein called melittin that has been modified to enable it to bind to a molecule called small interfering RNA (siRNA). The melittin delivers siRNA to the damaged joint, interfering with inflammation in cells.

Source: https://source.wustl.edu/

Vaccine That Is Programmable In One Week

MIT engineers have developed a new type of easily customizable vaccine that can be manufactured in one week, allowing it to be rapidly deployed in response to disease outbreaks. So far, they have designed vaccines against Ebola, H1N1 influenza, and Toxoplasma gondii (a relative of the parasite that causes malaria), which were 100 percent effective in tests in mice. The vaccine consists of strands of genetic material known as messenger RNA, which can be designed to code for any viral, bacterial, or parasitic protein. These molecules are then packaged into a molecule that delivers the RNA into cells, where it is translated into proteins that provoke an immune response from the host.

In addition to targeting infectious diseases, the researchers are using this approach to create cancer vaccines that would teach the immune system to recognize and destroy tumors.

MIT-Program-Vaccines_0 (1)

This nanoformulation approach allows us to make vaccines against new diseases in only seven days, allowing the potential to deal with sudden outbreaks or make rapid modifications and improvements,” says Daniel Anderson, an associate professor in MIT’s Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES).

Anderson is the senior author of a paper describing the new vaccines in the Proceedings of the National Academy of Sciences. The project was led by Jasdave Chahal, a postdoc at MIT’s Whitehead Institute for Biomedical Research, and Omar Khan, a postdoc at the Koch Institute; both are the first authors of the paper.

Source: http://news.mit.edu/

How To Map RNA Molecules In The Brain

Cells contain thousands of messenger RNA molecules, which carry copies of DNA’s genetic instructions to the rest of the cell. MIT engineers have now developed a way to visualize these molecules in higher resolution than previously possible in intact tissues, allowing researchers to precisely map the location of RNA throughout cells. Key to the new technique is expanding the tissue before imaging it. By making the sample physically larger, it can be imaged with very high resolution using ordinary microscopes commonly found in research labs.

MIT RNA-Imaging

Now we can image RNA with great spatial precision, thanks to the expansion process, and we also can do it more easily in large intact tissues,” says Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT, a member of MIT’s Media Lab and McGovern Institute for Brain Research, and the senior author of a paper describing the technique in the July 4 issue of Nature Methods.

Studying the distribution of RNA inside cells could help scientists learn more about how cells control their gene expression and could also allow them to investigate diseases thought to be caused by failure of RNA to move to the correct location.

Source: http://news.mit.edu/

Blood Test Can Diagnose Pancreatic Cancer

Indiana University cancer researchers have found that a simple blood test might help diagnose pancreatic cancer, one of the most deadly forms of the disease.

In research published today in the American Journal of Gastroenterology, Murray Korc, M.D., Professor of Cancer Research at the Indiana University School of Medicine and a researcher at the Indiana University Melvin and Bren Simon Cancer Center, and colleagues found that several microRNAs – small RNA molecules — circulate at high levels in the blood of pancreatic cancer patients.

blood cells

This is a new finding that extends previous knowledge in this field,” Dr. Korc said. “The key new feature here is that there is a panel of microRNAs that can be measured accurately in the plasma component of blood to determine if a patient has pancreatic cancer.”

Specifically, the IU research team found that an increased expression of miRNA-10b, -155, and -106b in plasma appears highly accurate in diagnosing pancreatic ductal adenocarcinoma. Pancreatic ductal adenocarcinoma is by far the most common type of pancreatic malignancy.

Source: http://news.medicine.iu.edu/

How To Heal Diabetic Skin Wounds

A new high-tech but simple ointment applied to the skin may one day help diabetic patients heal stubborn and painful ulcers on their feet, Northwestern University researchers report.

Scientist and dermatologist Amy S. Paller and chemist Chad A. Mirkin are the first to develop a topical gene regulation technology that speeds the healing of ulcers in diabetic animals. They combined spherical nucleic acids (SNAs, which are nanoscale globular forms of RNA) with a common commercial moisturizer to create a way to topically knock down a gene known to interfere with wound healing.

Type 2 diabetes and its enormous associated costs are on the rise in the United States. More than one-fifth of the 27 million type 2 diabetics in the country have chronic, non-healing skin wounds, and many undergo amputation. The Northwestern discovery offers a possible solution to this serious problem.
Finding a new way to effectively heal these resistant diabetic wounds is very exciting,” said Dr. Paller, director of Northwestern’s Skin Disease Research Center. “But, in addition, this study further proved that SNAs — in nothing but common moisturizer — can penetrate the skin barrier, a challenge that other therapies have been unable to conquer.

Source: http://www.northwestern.edu/

Cell Reprogramming

In 1953 Watson and Crick first published the discovery of the double helix structure of the DNA. They were able to visualize the DNA structure by means of X-Ray diffraction. Techniques, such as electron microscopy, allowed scientists to identify nucleosomes, the first and most basic level of chromosome organisation. Until now it was known that our DNA is packaged by regular repeating units of those nucleosomes throughout the genome giving rise to chromatin. However, due to the lack of suitable techniques and instruments, the chromatin organisation inside a cell nucleus could not be observed in a non-invasive way with the sufficient resolution. Now, for the first time, a group of scientists at the Center for Genomic Regulation CRG and ICFO in Barcelona (Spain), have been able to visualise and even count the smallest units which, packaged together, form our genome. This study was possible thanks to the use of super-resolution microscopy, a new cutting-edge optical techniquethat received the Nobel Prize in Chemistry in 2014. In combination with innovative quantitative approaches and numerical simulations, they were also able to define the genome architecture at the nano-scale. Most importantly, they found that the nucleosomes are assembled in irregular groups across the chromatin and nucleosome-free-DNA regions separate these groups.
Genome Sequencing

By using the STORM technique, a new super-resolution microscopy method, we have been able to view and even count nucleosomes across the chromatin fibers and determine their organisation. STORM overcomes the diffraction limit that normally restricts the spatial resolution of conventional microscopes and enables us to precisely define the chromatin fibre structure”, states Prof. Melike Lakadamyali, group leader at ICFO.This enabling technique allowed the researchers to go deeper and, by comparing stem cells to Differentiated cells (specialised cells that have already acquired their role), they observed key differences in the chromatin fibre architectures of both cells.

We found that stem cells have a different chromatin structure than somatic (specialised) cells. At the same time, this difference correlates with the level of pluripotency. The more pluripotent a cell is, the less dense is its packaging. It gives us new clues to understand the stem cells functioning and their genomic structure, which will be helpful for example, in studying cell reprogramming”, explains Pia Cosma, group leader and ICREA research professor at the CRG.
Source: http://www.crg.eu/en/

Medical Nanorobots

Researchers from the Institute of General Physics, the Institute of Bioorganic Chemistry (Russia, Academy of Sciences) and MIPT have made an important step towards creating medical nanorobots. They discovered a way of enabling nano– and microparticles to produce logical calculations using a variety of biochemical reactions.
biological nanorobotsThe scientists draw on the idea of computing using biomolecules. In electronic circuits, for instance, logical connectives use current or voltage (if there is voltage, the result is 1, if there is none, it’s 0). In biochemical systems, the result can a given substance. For example, modern bioengineering techniques allow for making a cell illuminate with different colors or even programming it to die, linking the initiation of apoptosis to the result of binary operations.

Scientists say logical operations inside cells to be a way of controlling biological processes and creating nano-robots, which can deliver drugs on schedule. Calculations using biomolecules inside cells, a.k.a. biocomputing, are a very promising and rapidly developing branch of science, according to the leading author of the study, Maxim Nikitin, a 2010 graduate of MIPT’s Department of Biological and Medical Physics. Biocomputing uses natural cellular mechanisms.

The study paves the way for a number of biomedical technologies and differs significantly from previous works in biocomputing binary operations in DNA, RNA and proteins for over a decade now, but Maxim Nikitin and his colleagues were the first to propose and experimentally confirm a method to transform almost any type of nanoparticle or microparticle into autonomous biocomputing structures that are capable of implementing a functionally complete set of Boolean logic gates (YES, NOT, AND and OR) and binding to a target (such as a cell) as result of a computation.

The prefix “nano” in this case is not a fad or a mere formality. A decrease in particle size sometimes leads to drastic changes in the physical and chemical properties of a substance. The smaller the size, the greater the reactivity; very small semiconductor particles, for example, may produce fluorescent light. The new research project used nanoparticles (i.e. particles of 100 nm) and microparticles (3000 nm or 3 micrometers).

The new work was published on the website of the journal Nature Nanotechnology.
Source: http://mipt.ru/

RNA Silences Genes, Treats Cancer

RNA interference (RNAi), a technique that can turn off specific genes inside living cells, holds great potential for treating many diseases caused by malfunctioning genes. RNA, a nanoparticle, transfers information from DNA to protein-forming system of the cell. However, it has been difficult for scientists to find safe and effective ways to deliver gene-blocking RNA to the correct targets.
Up to this point, researchers have gotten the best results with RNAi targeted to diseases of the liver, in part because it is a natural destination for nanoparticles. But now, in a study appearing in the May 11 issue of Nature Nanotechnology, an MIT-led team reports achieving the most potent RNAi gene silencing to date in nonliver tissues.
Using nanoparticles designed and screened for endothelial delivery of short strands of RNA called siRNA, the researchers were able to target RNAi to endothelial cells, which form the linings of most organs. This raises the possibility of using RNAi to treat many types of disease, including cancer and cardiovascular disease, the researchers say.

MIT engineers designed RNA-carrying nanoparticles (red) that can be taken up
There’s been a growing amount of excitement about delivery to the liver in particular, but in order to achieve the broad potential of RNAi therapeutics, it’s important that we be able to reach other parts of the body as well,” says Daniel Anderson, the Samuel A. Goldblith Associate Professor of Chemical Engineering, a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science, and one of the paper’s senior authors.
The paper’s other senior author is Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute. Lead authors are MIT graduate student James Dahlman and Carmen Barnes of Alnylam Pharmaceuticals.

Source: http://newsoffice.mit.edu/

How To Measure Cancer In Living Cells

Purdue University researchers have developed a way to detect and measure cancer levels in a living cell by using tiny gold particles with tails of synthetic DNA. A team led by Joseph Irudayaraj, professor of agricultural and biological engineering, used gold nanoparticles to target and bind to fragments of genetic material known as BRCA1 messenger RNA splice variants, which can indicate the presence and stage of breast cancer. The number of these mRNA splice variants in a cell can be determined by examining the specific signal that light produces when it interacts with the gold nanoparticles.

A single gold nanoparticle, or monomer, appears green when illuminated (top left), while a pair of gold nanoparticles bound to an mRNA splice variant, or dimer, appears reddish (top right). Monomers and dimers also scatter light differently, as shown in the graph above

This is a simple yet sophisticated technique that can be used to detect cancer in a single cell and determine how aggressive it is,” said Irudayaraj, who is also the deputy director of the Bindley Bioscience Center. “Being able to quantify these genetic molecules could ultimately help clinicians provide better and more individualized treatment to cancer patients.”

The technique also could increase our understanding of cell biology and paves the way for genetic profiling and diagnosis based on a single cell, Irudayaraj said.
Source: http://www.purdue.edu/

How To Detect Dengue Virus At Low Cost

University of Notre Dame biologists are reporting the development of an easy-to-use, low-cost method of detecting dengue virus in mosquitoes based on gold nanoparticles. Their research is published in the Virology Journal this week. The assay they have developed is able to detect lower levels of the virus than current tests, and is easy to transport and use in remote regions.
Dengue Virus
Half of the world’s population is at risk of dengue virus infection. The disease infects 50 million to 100 million people per year. Approximately one half-million of those affected require hospitalization, and many of the infected children will die. The dengue virus is one of the most dangerous viruses in the world with no available vaccine, and it does not respond to antiviral therapy. The main method of controlling infection remains the destruction of the standing water where the mosquitoes breed.

Source: http://news.nd.edu/news/