There are lessons to be learned from venoms.
Scorpions, snakes, snails, frogs and other creatures are thought to produce tens or even hundreds of millions of distinct venoms. These venoms have been honed to strike specific targets in the body.
For victims of a scorpion’s sting, that spells doom. For scientists, however, the potent molecules in venoms hold the potential to be adapted into medicines. But venoms are difficult to isolate and analyze using traditional methods, so only a handful have been turned into drugs.
Now a team led by scientists at The Scripps Research Institute (TSRI) has invented a method for rapidly identifying venoms that strike a specific target in the body—and optimizing such venoms for therapeutic use.
The researchers demonstrated the new method by using it to identify venoms that block a certain protein on T cells—a protein implicated in multiple sclerosis, rheumatoid arthritis and other inflammatory disorders. The researchers then used their method to find an optimized, long-acting variant of a venom that blocks this protein and showed that the new molecule powerfully reduces inflammation in mice.
“Until now we haven’t had a way to seriously harness venoms’ vast therapeutic potential,” said principal investigator Richard A. Lerner, Lita Annenberg Hazen Professor of Immunochemistry at TSRI.
The report on the advance by Lerner and his colleagues was selected as a “Hot Paper” and cover story by the journal Angewandte Chemie.
Choose Your Poison
The use of venoms as therapies may seem paradoxical, since these molecules generally evolved to harm and kill other organisms. But a low dose delivered to the right place can sometimes have highly beneficial effects. The pain-killing drug ziconotide (Prialt®), for example, is derived from one of the venoms used by cone-snails to immobilize their fishy prey. Venoms also are attractive from a drug development perspective because they tend to hit their targets on cells with very high potency and selectivity.
The Scripps Research Institute (TSRI) is a nonprofit American medical research facility that focuses on research and education in the biomedical sciences.
Headquartered in San Diego, California with a sister facility in Jupiter, Florida, the institute is home to 3,000 scientists, technicians, graduate students, and administrative and other staff, making it among the largest private, non-profit biomedical research organizations in the world.
TSRI’s California campus is located on 35 acres (140,000 m2) of land between the Torrey Pines State Reserve and the University of California, San Diego in La Jolla. In Florida, TSRI occupies 30 acres (120,000 m2) adjacent to the John D. MacArthur campus of Florida Atlantic University in Palm Beach County, Florida.
The Florida campus of TSRI operates a 350,000-square-foot (33,000 m2) state-of-the-art biomedical research facility focusing on neuroscience, cancer biology, medicinal chemistry, drug discovery, biotechnology, and alternative energy development. Approximately 450 faculty, staff and students occupy TSRI’s Florida campus. TSRI Florida is housed on the Jupiter campus of Florida Atlantic University.
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The Scripps Research Institute research articles from Innovation Toronto
- New Method Opens Door to Development of Many New Medicines – June 16, 2016
- New Method Enlists Electricity for Easier, Cheaper, Safer Chemistry – May 11, 2016
- A Cheap, Portable Drug-Discovery System: LIGHTSABR – February 14, 2016
- Scripps Florida Scientists Reveal Potential Treatment for Life-Threatening Viral Infections – November 25, 2015
- Cancer Treatment Breakthrough: Researchers Engineer A Way To Make Leukemia Cells Kill Each Other – October 23, 2015
- Progress towards a universal, and perhaps, lifelong flu vaccine – August 30, 2015
- Scripps Research, Mayo Clinic Scientists Find New Class of Drugs that Dramatically Increases Healthy Lifespan – March 10, 2015
- Scientists Announce Anti-HIV Agent So Powerful It Can Work in a Vaccine – February 19, 2015
- Scientists Open New Frontier of Vast Chemical ‘Space’ – December 21, 2014
- Scripps Florida Scientists Make Diseased Cells Synthesize Their Own Drug – September 6, 2014
- Scripps Research Institute Chemists Uncover Powerful New Click Chemistry Reactivity – August 18, 2014
- Scientists Add Letters to DNA’s Alphabet, Raising Hope and Fear | synthetic biology – May 8, 2014
- Scripps Research Institute Scientists Create First Living Organism that Transmits Added Letters in DNA ‘Alphabet’ | DNA biology – May 7, 2014
- Scientists find new way to upgrade natural gas
- Scripps Research Institute Scientists Identify First Potentially Effective Therapy for Human Prion Disease
- Innovative Screening Strategy Swiftly Uncovers New Drug Candidates, New Biology | drug-discovery strategy
- Clinical Trial Indicates Gabapentin Is Safe and Effective for Treating Alcohol Dependence
- New Strategy to Treat Multiple Sclerosis Shows Promise in Mice
- Scripps Florida Scientists Identify Potential New Drug for Inherited Cancer
- Drug Candidate Leads to Improved Endurance
- New Drug Candidate Has Dramatic Effect on Endurance
- New Compound Excels at Killing Persistent and Drug-Resistant Tuberculosis
- Chemists Invent Powerful Toolkit, Accelerating Creation of Potential New Drugs
- Meth Vaccine Shows Promising Results in Early Tests
- New ‘Biopsy in a Blood Test’ to Detect Cancer
- Discovery May Lead to Safer Treatments for Asthma, Allergies and Arthritis
- First Stem Cells from Endangered Species
- Can a vaccine stop drug abuse?
- Addicted to Fat: Overeating May Alter the Brain as Much as Hard Drugs
Carbon-Carbon Coupling Made Easy
Scientists at The Scripps Research Institute (TSRI) have devised a new molecule-building method that is likely to have a major impact on the pharmaceutical industry and many other chemistry-based enterprises.
The method, published as an online First Release paper in Science on April 21, 2016, allows chemists to construct novel, complex and potentially very valuable molecules, starting from a large class of compounds known as carboxylic acids, which are relatively cheap and non-toxic. Carboxylic acids include the amino acids that make proteins, fatty acids found in animals and plants, citric acid, acetic acid (vinegar) and many other substances that are already produced in industrial quantities.
“This is one of the most useful methods we have ever worked with, and it mostly involves materials that every chemist has access to already, so I think the interest in it will expand rapidly,” said principal investigator Phil S. Baran, Darlene Shiley Professor of Chemistry at TSRI.
“This exciting new discovery represents a significant advance in our ability to transform simple organic molecules and to rapidly build complex structures from readily available materials—we expect to use it in both the discovery and development of biologically active compounds that help patients prevail over serious disease,” said co-author Martin D. Eastgate, a Director in Chemical and Synthetic Development at Bristol-Myers Squibb, who participated in the study as part of a long-standing research collaboration between Bristol-Myers Squibb and TSRI.
A new study led by scientists at The Scripps Research Institute (TSRI) reveals a previously unknown type of immune cell. The discovery opens new avenues in the effort to develop novel therapies for autoimmune diseases such as type 1 diabetes.
The newly discovered cells resemble conventional T cells, yet are biased toward becoming T regulatory cells (Tregs), which protect the body from autoimmune disease.
“This study was eye-opening,” said study senior author and TSRI biologist Oktay Kirak. “You wouldn’t expect these cells to have this ability. The best analogy I have is Clark Kent turning into Superman. Clark Kent looks like an Average Joe, so no one would expect him to have the same abilities as Superman.”
Stopping Type 1 Diabetes
The body has an army of millions of immune cells. These cells contain receptors generated through random genetic rearrangements–a clever strategy to keep them ready to fight unfamiliar viruses and bacteria. This diverse pool leaves many questions for scientists, however, about which ones are active in specific diseases.
One puzzling disease is type 1 diabetes, in which immune cells mistakenly attack insulin-producing cells in the pancreas. Scientists know that Tregs should be able control this autoimmune response, deflecting the attack. Current clinical trials are focusing on increasing the numbers of Treg cells and finding ways to make them enter the pancreas.
In the new study, researchers began to solve this problem by isolating an individual Treg from a mouse model of type 1 diabetes and inserting its nucleus–which contained the unique genetic immune receptor information–into a mouse egg cell that had its own nucleus removed.
Using this cloning method (Somatic Cell Nuclear Transfer), the scientists created a mouse model that produced only the original Treg, allowing them to study its origins and functions for the first time.