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Archive - Mar 30, 2017

MIT Researchers Program RNA Vaccine That Could Protect Against Zika Virus

Using a new strategy that can rapidly generate customized RNA vaccines, MIT researchers have devised a new vaccine candidate for the Zika virus. The vaccine consists of strands of messenger RNA that are packaged into a nanoparticle that delivers the RNA into cells. Once inside cells, the RNA is translated into proteins that provoke an immune response from the host, but the RNA does not integrate itself into the host genome, making it potentially safer than a DNA vaccine or vaccinating with the virus itself. “It functions almost like a synthetic virus, except it’s not pathogenic and it doesn’t spread,” says Dr. Omar Khan, a postdoc at MIT’s Koch Institute for Integrative Cancer Research and an author of the new study. “We can control how long it’s expressed, and it is RNA so it will never integrate into the host genome.” This research also yielded a new benchmark for evaluating the effectiveness of other Zika vaccine candidates, which could help others who are working toward the same goal. Dr. Jasdave Chahal, a postdoc at MIT’s Whitehead Institute for Biomedical Research, is the first author of the paper, which was published online on March 21, 2017 in Scientific Reports. The paper’s senior author is Dr. Hidde Ploegh, a former MIT biology professor and Whitehead Institute member who is now a senior investigator in the Program in Cellular and Molecular Medicine at Boston Children’s Hospital. Other authors of the paper are Dr. Tao Fang and Dr. Andrew Woodham, both former Whitehead Institute postdocs in the Ploegh lab; Jingjing Ling, an MIT graduate student; and Daniel Anderson, an associate professor in MIT’s Department of Chemical Engineering and a member of the Koch Institute and MIT’s Institute for Medical Engineering and Science (IMES).

Panacea Pharmaceuticals Will Present Data That Its Cancer Biomarker HAAH Is Readily Detectable in Serum Exosomes

On March 30, 2017, Panacea Pharmaceuticals, Inc. announced that a paper regarding detection of the cancer biomarker HAAH [human aspartyl (asparaginyl) beta hydroxylase] will be presented at the annual American Association for Cancer Research (AACR) meeting in Washington, D.C., held April 1-5, 2017. The paper is titled: "Improved Detection of Cancer Specific Serum Exosomal Aspartyl (Asparaginyl) Beta Hydroxylase (HAAH)." The paper demonstrates major refinements to Panacea's multi-cancer HAAH-exosome detection assay that targets the cancer-specific blood serum biomarker HAAH. The cancer field is intensely focused upon exosomes, which are nanoparticle-sized sub-cellular vesicles derived from cancer cells that are proving to be important biomarkers and mediators of cancer cell metastasis and progression. The company asserts that the association of Panacea's target molecule HAAH with exosomes has led to a better individual understanding of these biomarkers as well as further development of a markedly improved diagnostic test with higher sensitivity and specificity than previous versions of the assay. "We are excited to report our continued advances in the understanding of the role of serum exosomes in the detection and monitoring of cancer," said Hossein Ghanbari, Ph.D., CEO and CSO of Panacea. Panacea Pharmaceuticals, headquartered in Gaithersburg, Maryland, is a clinical-stage biopharmaceutical company developing novel biologically targeted cancer therapies and diagnostics for unmet medical need.

New Study Establishes Evolutionary Origin of Photosynthesis in Cyanobacteria

The ability to generate oxygen through photosynthesis--that helpful service performed by plants and algae, making life possible for humans and animals on Earth--evolved just once, roughly 2.3 billion years ago, in certain types of cyanobacteria. This planet-changing biological invention has never been duplicated, as far as anyone can tell. Instead, according to “endosymbiotic theory,” all the "green" oxygen-producing organisms (plants and algae) simply subsumed cyanobacteria as organelles in their cells at some point during their evolution. "Oxygenic photosynthesis was an evolutionary singularity," says Woodward Fischer, Ph.D., Professor of Geobiology at Caltech, referring to the process by which certain organisms use the energy of sunlight to convert carbon dioxide and water into sugar for food, with oxygen as a by-product. "Cyanobacteria invented it, and then ultimately become the chloroplasts of algae. Plants are just a group of algae that moved on land." Yet, as world-shaping as cyanobacteria are, relatively little is known about them. Until a couple of decades ago, they were called "blue-green algae" by taxonomists, though it was later revealed that they are not algae at all, but rather a completely different type of organism. That lack of taxonomic understanding made deciphering the riddle of their evolution all but impossible, Dr. Fischer says. "For the longest time, they were just their own group. We had no answer about where they came from, or what other organisms they were related to," Dr. Fischer says. "Imagine trying to understand something about human evolution without knowledge of the great apes." Publishing in the March 31, 2017 issue of Science, Dr. Fischer and colleagues from Caltech and the University of Queensland in Australia have finally fleshed out cyanobacteria's family tree.

Scientists Model a Genetic Neurological Disease (PMD) with Oligodendrocytes Derived from Induced Pluripotent Stem Cells (iPSCs)

Researchers at the Case Western Reserve University School of Medicine in Cleveland have successfully grown stem cells from children with a devastating neurological disease to help explain how different genetic backgrounds can cause common symptoms. The work sheds light on how certain brain disorders develop, and provides a framework for developing and testing new therapeutics. Medications that appear promising when exposed to the new cells could be precisely tailored to individual patients based on their genetic background. In the new study, published online on March 30, 2017 in The American Journal of Human Genetics, researchers used stem cells in their laboratory to simultaneously model different genetic scenarios that underlie neurologic disease. They identified individual and shared defects in the cells that could inform treatment efforts. The open-access AJHG article is titled “Modeling the Mutational and Phenotypic Landscapes of Pelizaeus-Merzbacher Disease with Human iPSC-Derived Oligodendrocytes.” The researchers developed programmable stem cells, called induced pluripotent stem cells (iPSCs), from 12 children with various forms of Pelizaeus-Merzbacher disease (PMD). The rare, but often fatal, genetic disease can be caused by one of hundreds of mutations in a gene critical to the proper production of nerve cell insulation, or myelin. Some children with PMD have missing, partial, duplicate, or even triplicate copies of this gene, while others have only a small mutation. With so many potential causes, researchers have been in desperate need of a way to accurately and efficiently model genetic diseases like PMD in human cells. By recapitulating multiple stages of the disease in their laboratory, the researchers established a broad platform for testing new therapeutics at the molecular and cellular level.

Molecular Exchange Mediated by Microvesicles (MVs) Can Drive Acquisition of Phage Sensitivity by Normally Resistant Bacteria (R Cells) Co-Cultured with Infected Sensitive Bacteria (S Cells); Implications for Bacterial Genome Evolution

Scientists at The Hebrew University’s Institute of Medical Research Israel-Canada have made the unexpected observation that normally phage-resistant bacteria (R cells) can occasionally be invaded by phage when the R cells are cultured together with infected phage-sensitive bacteria (S cells). They termed this phenomenon “acquisition of sensitivity” (ASEN) and showed that it is mediated by the R cells transiently gaining phage attachment molecules from neighboring S cells. They further provided evidence that this molecular exchange is driven by microvesicles (MVs) containing phage attachment molecules that are released from infected S cells. The researchers suggest that this raises the possibility that such a mechanism facilitates transduction events among species by a plethora of phages, even by those having a narrow host range. They note that such multispecies transductions could prime horizontal gene transfer and, consequently, bacterial genome evolution. Phage invasion into R cells could have a major impact on the transfer of antibiotic resistance and virulence genes among bacteria. The scientists write that this possibility should be carefully considered when employing phage therapy, as phage infection of a given species may result in gene transmission into neighboring bacteria resistant to the phage. This research was published in the January 12, 2017 issue of Cell. The article is titled “Acquisition of Phage Sensitivity by Bacteria through Exchange of Phage Receptors.” Philip Askenase, M.D., Professor of Medicine & Pathology at the Yale University School of Medicine, made the following comment on the significance of this work: "Such a fundamental event in such a basic system by MVs speaks to their universality and the fundamental nature of their transfers." Dr. Askenase was not involved in the research.