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!
Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München
Second research flight into zero gravity
21.10.2016 | Universität Zürich
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences