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

February 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: The surprising role of gene architecture in cell fate decisions

Related Stories

The surprising role of gene architecture in cell fate decisions

January 16, 2018
Scientists read the code of life—the genome—as a sequence of letters, but now researchers have also started exploring its three-dimensional organisation. In a paper published in Nature Genetics, an interdisciplinary research ...

Blood-vessel-on-a-chip provides insight into new anti-inflammatory drug candidate

January 15, 2018
One of the most important and fraught processes in the human body is inflammation. Inflammatory responses to injury or disease are crucial for recruiting the immune system to help the body heal, but inflammation can also ...

Study advances gene therapy for glaucoma

January 16, 2018
While testing genes to treat glaucoma by reducing pressure inside the eye, University of Wisconsin-Madison scientists stumbled onto a problem: They had trouble getting efficient gene delivery to the cells that act like drains ...

'Decorated' stem cells could offer targeted heart repair

January 10, 2018
Although cardiac stem cell therapy is a promising treatment for heart attack patients, directing the cells to the site of an injury - and getting them to stay there - remains challenging. In a new pilot study using an animal ...

What are antioxidants? And are they truly good for us?

January 11, 2018
Antioxidants seem to be everywhere; in superfoods and skincare, even chocolate and red wine. Products that contain antioxidants are marketed as essential for good health, with promises to fight disease and reverse ageing.

How can CRISPR genome editing shape the future of cancer research?

January 12, 2018
The genome editing technology CRISPR is causing plenty of excitement in cancer research.

Recommended for you

How metal scaffolds enhance the bone healing process

January 22, 2018
A new study shows how mechanically optimized constructs known as titanium-mesh scaffolds can optimize bone regeneration. The induction of bone regeneration is of importance when treating large bone defects. As demonstrated ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

1 comment

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.