Researchers at Duke University Medical Center have devised a way they might deliver the right therapy directly to tumors using special molecules, called aptamers, which specifically bind to living tumor tissue.
They screened a large pool of aptamers in a rodent with liver cancer until they found the best molecule to bind to a tumor protein.
"We are already exploring attaching chemicals to the aptamers, so the aptamer molecules could deliver tumor-killing agents where they are needed, which is the next phase of our research," said senior author Bryan Clary, M.D., chief of the Division of Hepatopancreatobiliary and Oncologic Surgery.
The study was published in Nature Chemical Biology online on Nov. 29.
Aptamers are small pieces of RNA that bind to a specific target molecule, usually a protein. They offer ease of use because they can be easily regenerated and modified and therefore have increased stability over some other agents, such as protein-based antibodies. Notably, they have a very low chance of immune-system interference, making them great candidates for tumor diagnosis and therapy.
"Most importantly, it's not necessary to have detailed knowledge of protein changes in the disease before the selection process," said lead author Jing Mi, M.D., Ph.D., assistant professor in the Duke Department of Surgery. "This greatly simplifies the process of molecular probe development. The selected aptamers can be used to discover proteins not previously linked with the disease in question, which could speed up the search for effective therapies."
The researchers used a large pool of RNA strands and applied them to a rodent with a liver tumor, the type of metastatic tumor that often results from a colon cancer tumor.
"We hypothesized that the RNA molecules that bind to normal cellular elements would be filtered out, and this happened," said Clary, who treats colon cancer patients. "In this way, we found the RNA molecules that went specifically to the tumor."
The researchers removed the tumor, extracted the specific RNA in the tumor, amplified these pieces of RNA to create a greater amount, and reinjected the molecules to learn which bound most tightly to the tumor. They repeated this process 14 times to find a good candidate.
The team found a tumor-targeting RNA aptamer that specifically bound to RNA helicase p68, a nuclear protein produced in colorectal tumors.
"This aptamer not only binds to p68 protein in cell culture, but also preferentially binds to cancer deposits in a living animal," Mi said. "The nice thing about this aptamer approach is that it could be used to discover the molecular signatures of many other diseases."
Clary said the process could be repeated with different types of tumors. For example, a scientist might take a breast cancer line and grow it in the lung as a metastasis model and then perform in vivo selection to identify RNAs specifically binding to the lung tumor.
"This would work, theoretically," Clary said. "The idea of selecting molecules targeting a tumor growing in a body that results in a useful reagent for biologic exploration and therapy delivery in tumors is exciting."
In fact, based on earlier research done with proteins called peptides, the researchers expected that the aptamer process would find proteins in the blood vessels feeding the liver tumor, but instead they found the p68 target inside of tumor cells. "We think this is a valuable target because delivering to the sites inside of cells may make it easier to treat an entire tumor with drugs that are 'escorted' by the aptamer," Clary said.
He said that repeating the selection and amplification process with the same liver tumor could lead to development of other aptamers that bind well to proteins in tumor tissue besides p68. The team focused its initial efforts on developing an escort for p68 because this protein was known to be overexpressed in colon cancer.
Other authors include Yingmiao Liu, Johannes Urban and Bruce A. Sullenger of the Duke Department of Surgery, Zahid N. Rabbani of the Duke Department of Radiation Oncology, and Zhongguang Yang of the Moses Cone Memorial Hospital Department of Internal Medicine.
The study was funded by the Elsa U. Pardee Foundation, an American Cancer Society pilot award, and National Institutes of Health grants.
Mary Jane Gore | EurekAlert!
Bacteria as pacemaker for the intestine
22.11.2017 | Christian-Albrechts-Universität zu Kiel
Researchers identify how bacterium survives in oxygen-poor environments
22.11.2017 | Columbia University
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
22.11.2017 | Business and Finance
22.11.2017 | Physics and Astronomy
22.11.2017 | Physics and Astronomy