Nov 11, 2019
CRISPR: the movie
Posted by Klaus Baldauf in categories: biotech/medical, education, genetics
New gene-editing documentary showcases biology’s hottest tool — up to the point when things went awry. By Amy Maxmen.
New gene-editing documentary showcases biology’s hottest tool — up to the point when things went awry. By Amy Maxmen.
While the public is still imagining the future to be very much like the past, the researchers at the forefront of genetics are planning to redesign human bodies, to make us more long-lived, more resilient to disease, more strong and (I hope) more intelligent.
In a talk at Exponential Medicine, Jane Metcalfe said that tools like gene editing and synthetic biology could make design the next big thing in medicine.
Biology encodes information in DNA and RNA, which are complex molecules finely tuned to their functions. But are they the only way to store hereditary molecular information? Some scientists believe life as we know it could not have existed before there were nucleic acids, thus understanding how they came to exist on the primitive Earth is a fundamental goal of basic research. The central role of nucleic acids in biological information flow also makes them key targets for pharmaceutical research, and synthetic molecules mimicking nucleic acids form the basis of many treatments for viral diseases, including HIV. Other nucleic acid-like polymers are known, yet much remains unknown regarding possible alternatives for hereditary information storage. Using sophisticated computational methods, scientists from the Earth-Life Science Institute (ELSI) at the Tokyo Institute of Technology, the German Aerospace Center (DLR) and Emory University explored the “chemical neighbourhood” of nucleic acid analogues. Surprisingly, they found well over a million variants, suggesting a vast unexplored universe of chemistry relevant to pharmacology, biochemistry and efforts to understand the origins of life. The molecules revealed by this study could be further modified to gives hundreds of millions of potential pharmaceutical drug leads.
Nucleic acids were first identified in the 19th century, but their composition, biological role and function were not understood by scientists until the 20th century. The discovery of DNA’s double-helical structure by Watson and Crick in 1953 revealed a simple explanation for how biology and evolution function. All living things on Earth store information in DNA, which consists of two polymer strands wrapped around each other like a caduceus, with each strand being the complement of the other. When the strands are pulled apart, copying the complement on either template results in two copies of the original. The DNA polymer itself is composed of a sequence of “letters,” the bases adenine (A), guanine (G), cytosine © and thymine (T), and living organisms have evolved ways to make sure during DNA copying that the appropriate sequence of letters is almost always reproduced. The sequence of bases is copied into RNA by proteins, which then is read into a protein sequence.
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The tiny hydra, a freshwater invertebrate related to jellyfish and corals, has an amazing ability to renew its cells and regenerate damaged tissue. Cut a hydra in half, and it will regenerate its body and nervous system in a couple of days. Researchers at the University of California, Davis have now traced the fate of hydra’s cells, revealing how three lines of stem cells become nerves, muscles or other tissues.
Celina Juliano, assistant professor in the UC Davis Department of Molecular and Cellular Biology, project scientist Stefan Siebert and colleagues including Jeff Farrell, a postdoctoral researcher at Harvard University, sequenced the RNA transcripts of 25,000 single hydra cells to follow the genetic trajectory of nearly all differentiated cell types.
“The beauty of single-cell sequencing and why this is such a big deal for developmental biologists is that we can actually capture the genes that are expressed as cells differentiate from stem cells into their different cell types,” Juliano said.
The philosophy that we should merge with machines to expand our intelligence and extend life is gaining traction. Design, scientific and technological frontiers are being pushed to redefine nature through AI, AR, biotech, genetics, and VR.
Questionable startups are claiming to be able to determine how smart a frozen IVF embryo will become if carried to term, and parents are taking the bait.
Genomic Prediction, the most prominent of these companies, offers tests to scan embryos for genetic diseases and other conditions — as well as genetic indicators that a future child will be in the bottom two percent of intelligence.
And MIT Technology Review reports that Genomic Prediction co-founder Stephen Hsu often uses media appearances to discuss future plans for a general intelligence test — something that, with current tech, is extremely unlikely to actually work.
City of Hope researchers may have found a way to sharpen the fastest, cheapest and most accurate gene editing technique, CRISPR-Cas9, so that it can more successfully cut out undesirable genetic information.
This improved cutting ability could one day fast-track potential therapies for HIV, sickle cell disease and, potentially, other immune conditions.
“Our CRISPR-Cas9 design may be the difference between trying to cut a ribeye steak with a butter knife versus slicing it with a steak knife,” said Tristan Scott, Ph.D., lead author of the study and a staff research scientist at City of Hope’s Center for Gene Therapy. “Other scientists have tried to improve CRISPR cutting through chemical modifications, but that’s an expensive process and is like diamond-coating a blade. Instead, we have designed a better pair of scissors you can buy at any convenience store.”
Gene therapy has traditionally been applied to well-understood diseases where a single genetic mutation was to blame. A new generation of technology is expanding the potential of gene therapy to treat conditions that were previously unreachable. Since the first gene therapy clinical trials in the 1990s, the technology has made its way into the market for conditions ranging from blindness to cancer. Gene therapy has the potential to fix any genetic mutation causing disease by inserting a new copy of the faulty gene. However, its reach has historically been limited. We’ve been constrained with the things we.
David A. Sinclair, PhD, is a professor in the Department of Genetics at Harvard Medical School and co-director of the Paul F. Glenn Center for the Biological Mechanisms of Aging.
Dr. Sinclair’s work focuses on understanding the mechanisms that drive human aging and identifying ways to slow or reverse aging’s effects. In particular, he has examined the role of sirtuins in disease and aging, with special emphasis on how sirtuin activity is modulated by compounds produced by the body as well as those consumed in the diet, such as resveratrol. His work has implications for human metabolism, mitochondrial and neurological health, and cancer.
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