Researchers say the advance, reported in the journal Cell, is potentially an important step in making human cancer both more visible and accessible to treatment; it may also allow prediction and monitoring of how specific anti-cancer agents are actually working.
"In tumor-bearing mice, we show that this hybrid virus can target tumors systemically to deliver an imaging or therapeutic gene," says the co-leader of the study, Renata Pasqualini, Ph.D., professor of Medicine and Cancer Biology. "The signal is specific only to tumors, so one can monitor drug effectiveness at the molecular level."
The team created and characterized the hybrid viruses by combining genetic elements and biological attributes of an animal virus (adeno-associated virus, or AAV) with those of a bacterial virus (phage). Unlike animal viruses that infect mammalian cells, bacterial viruses have evolved to infect only bacterial hosts. The paper shows how particles of the hybrid virus, called AAV phage or AAVP, can serve as a vehicle for targeted delivery of genes to experimental tumors in mice and to the tumors’ blood vessel supply, providing a strategy for finding tumors and genetically marking them for imaging on a clinic-ready body scanner.
The AAVP hybrid combines the ability of the bacterial virus to target specific tissues with the capability of the mammalian virus to actually deliver genes to cells. The crucial vehicles, or vectors, in the AAVP hybrid retained the properties of their respective parental viruses, which the researchers called a surprising outcome.
"This is only a proof-of-concept, and although we have yet to translate these hybrid viruses for use in humans, we hope that this new system will have future clinical applications," says Wadih Arap, M.D., the co-leader of the study and professor of Medicine and Cancer Biology. "In addition to the obvious biological interest, when the vector is refined for patient use, it could perhaps help us diagnose, monitor and treat human tumors more accurately."
The finding is the latest in a series of studies by Pasqualini and Arap that are built around their discovery that the human vasculature system contains unique molecular addresses. Organs and specialized tissues also have specific "zip codes" on their blood vessels, as do tumor blood vessels. Knowing this, Pasqualini and Arap designed, constructed, evaluated, and validated the targeted AAVP system over the past several years. Amin Hajitou, Ph.D., a post-doctoral fellow in the Arap/Pasqualini laboratory and first author of the Cell study says, "we were pleased by the strong effects of gene transfer in mouse models of common diseases such as breast and prostate cancer."
Their next step was to work closely with the team of M. D. Anderson researcher Juri Gelovani, M.D., Ph.D., chair of the Department of Experimental Diagnostic Imaging, a pioneer in development of molecular-genetic imaging tools.
"We could see by using positron emission tomography that the reporter and therapeutic genes were being expressed throughout the tumors in the animals," Gelovani says. "This is an example of the so-called "theragnostic" approach, a combination of the words therapeutic and diagnostic."
Next, the international collaborative research team plans to evaluate the safety and efficacy of other hybrid vectors in animal models. The ultimate goal is to adapt and optimize the AAVP-based targeting prototype for use in patients.
Nancy Jensen | EurekAlert!
Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo
Research reveals how order first appears in liquid crystals
23.05.2018 | Brown University
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
23.05.2018 | Materials Sciences
23.05.2018 | Physics and Astronomy
23.05.2018 | Life Sciences