Engineers create intelligent molecules that seek-and-destroy diseased cells

Feb 13, 2009

Current treatments for diseases like cancer typically destroy nasty malignant cells, while also hammering the healthy ones. Using new advances in synthetic biology, researchers are designing molecules intelligent enough to recognize diseased cells, leaving the healthy cells alone.

"We basically design molecules that actually go into the cell and do an analysis of the cellular state before delivering the therapeutic punch," said Christina Smolke, assistant professor of bioengineering who joined Stanford University in January.

"When you look at a diseased cell (e.g. a cancer cell) and compare it to a normal cell, you can identify biomarkers—changes in the abundance of proteins or other biomolecule levels—in the diseased cell," Smolke said. Her research team has designed molecules that trigger cell death only in the presence of such markers. "A lot of the trick with developing effective therapeutics is the ability to target and localize the therapeutic effect, while minimizing nonspecific side effects," she said.

Smolke will present the latest applications of her lab's work at the American Association for the Advancement of Science (AAAS) meeting in Chicago on Friday, Feb. 13.

These designer molecules are created through RNA-based technologies that Smolke's lab developed at the California Institute of Technology. A recent example of these systems, developed with postdoctoral researcher Maung Nyan Win (who joined Smolke in her move to Stanford), was described in a paper published in the Oct. 17, 2008, issue of Science.

"We do our design on the computer and pick out sequences that are predicted to behave the way we like," Smolke said. When researchers generate these sequences inside the operating system of a cell, they reprogram the cell and change its function. "Building these molecules out of RNA gives us a very programmable and therefore powerful design substrate," she said.

Smolke's team focuses on well-researched model systems in breast, prostate and brain cancers, including immunotherapy applications based on reprogramming human immune response to different diseases. The researchers work directly with clinicians at the City of Hope Cancer Center (a National Cancer Institute designated Comprehensive Cancer Center in Duarte, Calif.) that have ongoing immunotherapy trials for treating glioma, a severe type of brain cancer.

"Our goal is to make more effective therapies by taking advantage of the natural capabilities of our immune system and introducing slight modifications in cases where it is not doing what we would like it to do," Smolke said. She hopes to translate her technologies into intelligent cellular therapeutics for glioma patients in the next five years. "That's a very optimistic view," she said. "But so far things have been moving quickly."

The broader implications for using intelligent molecules in immunotherapy and gene therapy seem limitless. Researchers and doctors can use this approach by targeting a specific cellular function or behavior they want to control in a particular disease. Then they can identify signals indicative of viral infection, host immune response, or drugs the clinician is administering and engineer the molecules to change the cell function in response to those signals.

"In a lot of therapies, you have nonspecific side effects or you're balancing the desired effect of the therapy on diseased cells or infection with its undesired effects on the entire host," Smolke said. Current chemotherapy treatments for cancer, and even many gene therapies, have drastic and debilitating consequences for patients. The designer molecules provide a whole new targeting accuracy that should mitigate these side effects.

"This is all very front-end work," Smolke said. "We've just started to move these foundational technologies into these sorts of downstream medical applications, and so there is a lot to learn … which makes it that much more exciting."

Smolke's work is funded by the National Institutes of Health, National Science Foundation, Department of Defense and the Beckman Foundation.

At the AAAS meeting, Smolke will present her work alongside Drew Endy, assistant professor of bioengineering at Stanford University, as part of the Synthetic Life symposium.

Endy, who joined Stanford last fall, will discuss the societal and safety implications of molecular synthesis technology. This includes the consequences of researchers moving toward building registries for standard biological parts and the education aspects of iGEM—an international forum where student teams compete to design and assemble engineered machines using advanced genetic components and technologies—which has led to the training of a new generation of scientists and bioengineers. Stanford will be hosting its first iGEM team this year. Endy will also discuss his efforts, along with colleagues, to start fabrication facilities focused on churning out libraries of open-access biological parts and the resulting implications for biological engineering.

Source: Stanford University

Explore further: Radical vaccine design effective against herpes viruses

add to favorites email to friend print save as pdf

Related Stories

Scientists find clues to cancer drug failure

Mar 02, 2015

Cancer patients fear the possibility that one day their cells might start rendering many different chemotherapy regimens ineffective. This phenomenon, called multidrug resistance, leads to tumors that defy ...

Research could make blue jeans green

Feb 23, 2015

Who doesn't like blue jeans? They're practically wrinkle-proof. The indigo dye that provides their distinctive color holds up to detergents, but ages into that soft, worn look. No wonder the average American ...

Golden vehicle for drug delivery has hidden costs

Feb 18, 2015

One of the biggest ideas in treating disease involves material so small it isn't even visible. Miniscule gold particles – the size of several atoms – are being touted as vehicles to send drugs exactly ...

Recommended for you

Radical vaccine design effective against herpes viruses

1 hour ago

Herpes simplex virus infections are an enormous global health problem and there is currently no viable vaccine. For nearly three decades, immunologists' efforts to develop a herpes vaccine have centered on ...

Popular antioxidant likely ineffective, study finds

10 hours ago

The popular dietary supplement ubiquinone, also known as Coenzyme Q10, is widely believed to function as an antioxidant, protecting cells against damage from free radicals. But a new study by scientists at McGill University ...

New findings on 'key players' in brain inflammation

10 hours ago

Inflammation is the immune system's natural reaction to an 'aggressor' in the body or an injury, but if the inflammatory response is too strong it becomes harmful. For example, inflammation in the brain occurs ...

Gut microbial mix relates to stages of blood sugar control

Mar 05, 2015

The composition of intestinal bacteria and other micro-organisms—called the gut microbiota—changes over time in unhealthy ways in black men who are prediabetic, a new study finds. The results will be presented Friday ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

Phaze
not rated yet Feb 13, 2009
so who have they tested on

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.