Three new studies mark advances in drug discovery and in treatments of both cardiovascular diseases and cancer.
The three groups of scientists have come up with unique biotechnology methods that further their respective areas of research. Their work will appear in the November issue of the scientific journal Nature Biotechnology.
One group has christened a brand new field that, should it come to fruition, will be called "vironcology." The researchers are using viruses to kill cancer tumors and hope to soon begin clinical trials in humans.
Bioengineers have discovered a way to induce the body to grow new, healthy blood vessels. If the technique works in humans, it could be an alternative to cardiac bypass surgery.
Gene researchers have devised a method using yeast that they believe will screen drugs quickly and accurately. Testing in yeast is one step better than a petri dish, because it's a living organism that more precisely predicts the performance of drugs in humans.
Virus to kill cancer: Researchers at a biotech company in San Diego, California, have engineered a virus to kill cancer tumors and only cancer tumors.
Paul Shabram, senior investigator of the study and a scientist with Canji, a wholly owned subsidiary of Schering Plough, used a virus called the adenovirus.
The adenovirus is famous among scientists for its use as a vehicle for therapeutic genes in gene therapy, a field the company is also pursuing.
The adenovirus has been implicated in problems with gene therapy, including the death of 18-year-old Jesse Gelsinger in 1999.
But the researchers say they've developed a method that's so specific, only a small and therefore harmless dose will be necessary.
"The ability to distinguish between normal and tumor cells will allow us to use much lower doses," said Murali Ramachandra, a principal scientist at Canji who also participated in the study.
The researchers used the adenovirus because it can rapidly spread through, multiply in, and destroy cells. The trick was to engineer the virus to selectively replicate only in tumor cells.
To do this, the researchers focused on the p53 gene, which is found to have a mutation in almost half of all human cancers.
Normally, p53 acts like an emergency brake to cell growth, but it sometimes carries a mutation causing it to allow cells to grow out of control.
Shabram and Ramachandra engineered an adenovirus to replicate only in cells with malfunctioning p53.
The experiment worked well in mice. Other experts, who didn't participate in the study, were hopeful that the technique could be a good complement to existing chemotherapies.
But there is a sticky point for all researchers who work with the adenovirus. It does not replicate in mice, so the researchers had to graft human tumors into mice to test the therapy.
Since the adenovirus doesn't replicate in mice, they won't know if it might replicate in normal tissue of humans until they actually test it.
"That kind of data must come from humans," Shabram said.
Other experts were hopeful.
"Will this marriage of the disciplines of virology and oncology ... really yield new treatments for cancer?" wrote Richard Vile of the molecular medicine program at the Mayo Clinic in Rochester, Minnesota. "I think that we can have guarded confidence in a reply of 'Not yet, but soon.'"
Building better blood vessels: Researchers at the University of Michigan have developed a way to grow robust new blood vessels that could offer people an alternative to bypass surgery.
David J. Mooney of the Department of Biomedical Engineering and his colleagues have bioengineered a polymer that coaxes the body to grow its own blood vessels, a process called angiogenesis.
Mooney saw success in rats, and if it works in humans it would help people with heart disease as well as people with impaired blood flow in limbs due to various diseases, including diabetes.
Mooney's technique uses a genetic growth factor called VEGF. Other researchers are injecting VEGF intravenously to generate blood vessel tissue, but late-stage clinical trials are not as successful as hoped.
The other techniques use only VEGF -- but another growth factor called PDGF also plays an important role in growing blood vessels. Over the past five years, Mooney devised a method to deliver both growth factors together.
"This led us to propose that one needed to deliver the proteins locally, in a sustained manner (in our case from a polymer), and to combine in a particular sequence two of these drugs," Mooney said.
PDGF provides a sort of timed-release function: It slows the release of VEGF, maintaining the release for a longer period of time.
The rats grew larger and more mature blood vessels than rats that received only one of the growth factors.
"The exciting findings of Richardson et al. underscore the importance of paying attention to not only the type of angiogenic growth factor ... for angiogenesis, but also how and when they should be delivered," wrote Peter Carmeliet of the Flanders Interuniversity Institute for Biotechnology at the University of Leuven in Belgium.
Yeast can make beer and screen drugs: Researchers at the University of Washington in Seattle have come up with a way to use yeast as a biosensor for discovering drugs.
The same yeast that makes bread and beer, Saccharomyces cerevisiae, can also tell researchers whether a drug will work.
The researchers altered the yeast to contain a specific enzyme. Then they added a small molecule, such as a potential drug that would act against the enzyme, in the yeast.
When the researchers raised the temperature of the yeast, the yeast did not grow properly, which indicated that the drug was working by blocking the action of the enzyme.
This method could be used with a variety of different enzymes and drugs, experts say.
The technique, which was invented by Stanley Fields of the departments of Genetics and Medicine at the University of Washington, is superior to two other systems attempted previously using yeast, according to the researchers who wrote commentary that accompanies the article.
It promises to work with a wider variety of potential drugs, according to Susana Vidan and Michael Snyder of the department of molecular, cellular and developmental biology at Yale University.
"The system described in the present paper by Tucker and Fields is a generic biosensor that overcomes many of the shortcomings of the other two in vivo systems," Vidan and Snyder wrote.
It's important for researchers to test potential drugs in living organisms, such as yeast, experts say. In a petri dish, solubility and stability of the drug can be significantly different.
