Developing “guided missiles” to attack cancer: A podcast featuring a Stanford bioengineer

Photo by Allocer

Chemotherapy attacks cancer by killing cells that are rapidly dividing. But this leads to serious side effects, like intestinal upset and hair fallout, because these normal cells grow quickly.

So researchers like Jennifer Cochran, PhD, a professor and the chair of bioengineering at Stanford, are developing more targeted cancer therapies, dubbed “guided missiles.” She recently described her work to professor and radio show Russ Altman, MD, PhD, on an episode of the Sirius radio show The Future of Everything.

“We, and others, have developed novel proteins that can selectively target cancer cells and then we can attach cargo to them — this is where the missile analogy comes in,” Cochran told Altman. “The cargo that we attach, things like chemotherapy, can then be selectively targeted to the tumor.” The idea is to precisely deliver to the tumor a more poisonous dose than you could deliver systemically, she said.

One way to do this is to bioengineer antibodies, which are molecules that recognize and help neutralize foreign substances like bacteria. However, Cochran’s lab took a slightly different approach. She explained to Altman:

“As amazing as antibodies are, they can have some limitations in that they are very large in terms of molecular size so they have trouble wiggling into a tumor. So we’ve created smaller versions of tumor-targeting proteins that can hopefully penetrate into tumors better. And we’ve then chemically attached chemotherapy molecules to deliver a punch to the cancer cells.”

In order to develop these proteins, her team is expediting protein evolution in a test tube — making favorable properties that would normally evolve over millions of years happen in just a few weeks. To do this, the team uses genetic manipulation to create millions of slightly different protein variants, tests them with high-throughput screening in just a few hours, identifies the ones most desirable for a certain task, and then determines these variants’ DNA sequences.

For example, they used this evolutionary process on a peptide, a small fragment of protein, from the seeds of a plant known as a squirting cucumber to turn the molecule into a favorable drug scaffold. “We ran the protein through this evolution process to create a tumor-targeting protein that we then hooked the chemotherapy agents on to,” said Cochran.

Cochran’s group is also investigating immunotherapy applications for her proteins. She is teaming up with Dane Wittrup, PhD, a professor in chemical engineering and biological engineering at Massachusetts Institute of Technology, who has developed new ways to use the immune system. By combining Cochran’s tumor-targeting technology with Wittrup’s insights into immunotherapy, they are able to give a “one-two punch” and activate multiple factors of the immune system to more effectively attack cancer, she said.

Her research team is also interested in applying their work to other diseases. She explained to Altman:

“We’ve been applying them for cancer, but you can use the same approach to deliver therapies to other types of disease tissue. We have really only just scratched the surface of what we can do. A big driver of this has been the interdisciplinary culture of collaborative research at Stanford. We’ve been working together with physicians, clinicians, scientists, engineers and physicists to tackle really challenging problems.”

Cochran’s bioengineered proteins are not yet available to patients. However, some tumor-targeting molecules are already approved by the U.S. Food and Drug Administration and many more are in the pipeline. “There are a number of molecules that are FDA approved and you might have heard commercials for them,” she told Altman. “But they only work for a subset of patients. So the question is: how do we make them work better for a larger subset of patients?”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

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Stanford experts discuss the future of bioengineering

Bioengineering — described by Stanford professor and radio host Russ Altman, MD, PhD, as the manipulation of biological systems to solve problems in medicine, the environment and energy — was the focus of a recent episode of the Sirius radio show The Future of Everything. On hand was Stanford’s Drew Endy, PhD, an associate professor of bioengineering, who spoke with Altman about how to unlock bioengineering’s full potential.

Endy told Altman that bioengineering is already incredibly important to the economy, but challenges to further growth still remain. “Regardless of what type of engineer you are and what kinds of problems you’re trying to find solutions to, you have to navigate what I call the core design-build-test engineering cycle,” said Endy. “So how do we get better at navigating this cycle for living systems?”

He suggested that one answer is synthetic biology. “It became apparent that the core of the engineering cycle for living matter could be massively and systematically upgraded. We could separate design from construction by getting better at printing DNA from scratch, called DNA synthesis,” he told Altman. By making the process more efficient, he said, scientists should be able to more quickly and cheaply create new genes or even organisms with specialized functions.

Endy went on to explain how DNA synthesis works: “This is a technology that lets you go from information to physical DNA made from scratch. So you can think of it like a keyboard with just 4 keys: ATCG. You play the keys as you wish, and the machine makes from raw ingredients the DNA depending on how you press the keys.”

DNA synthesis is a critical tool for many applications, such as vaccine development, gene therapy and molecular engineering. Although it has existed for years, it is now more affordable. “In 2003, it cost me four dollars a letter to press each key. This year, it’s about four cents,” he said. This dramatic reduction in cost makes new research more accessible and scientists are getting systematically better at engineering biology, he told Altman.

Endy envisions a future where we’ve made the living world fully engineerable. However, he said this raises many questions on safety, biosecurity and ethics that we need to address.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Stanford engineers create artificial skin that can signal pressure sensation to brain

The device on the golden fingertip is the skin-like sensor developed by Stanford engineers. (Bao Lab)
The device on the golden fingertip is the skin-like sensor developed by Stanford engineers. (Bao Lab)

A hand without a sense of touch doesn’t really feel like a hand, many amputees describe. It’s more like a pliers that can be manipulated by sending signals from the brain to the prosthetic device. They dream of being able to delicately pick up a glass or to feel the touch of a loved one’s hand.

Stanford chemical engineering professor Zhenan Bao, PhD, and her team have spent a decade trying to help make this dream a reality, by developing a material that mimics skin and its sensory functions. Taking a big step towards this goal, they have now created a skin-like material that can tell the difference between a soft touch and a firm handshake.

Their artificial skin has two layers. The bottom layer acts as a circuit that transports pulses of electricity to nerve cells and translates these signals into biochemical stimuli that the nerve cells can detect. The top layer is a sensing mechanism composed of thin plastic embedded with billions of carbon nanotubes. When pressure is put on the plastic, the nanotubes are squeezed closer together enabling them to conduct electricity. What’s new is that the top layer can now detect pressure over the same range as human skin.

According to a Stanford news release:

This allowed the plastic sensor to mimic human skin, which transmits pressure information to the brain as short pulses of electricity, similar to Morse code. Increasing pressure on the waffled nanotubes squeezes them even closer together, allowing more electricity to flow through the sensor, and those varied impulses are sent as short pulses to the sensing mechanism. Remove pressure, and the flow of pulses relaxes, indicating light touch. Remove all pressure and the pulses cease entirely.

A paper describing Bao’s new research has just been published in Science. As Bao comments in the release, “We have a lot of work to take this from experimental to practical applications. But after spending many years in this work, I now see a clear path where we can take our artificial skin.”

This is a repost of my Scope blog story, courtesy of Stanford School of Medicine.