Berkeley: Losing a breast or a lung to cancer leaves a scar, both physical and emotional. But even a biopsy to determine if a tumor is cancerous, or to track a tumor’s response to drugs, brings short-term pain and can miss signs of metastasis. So, the possibility of a scalpel-free biopsy has been something of a holy grail — a way to relieve trauma, speed diagnosis and shrink medical bills.
non-surgical approach might start with a simple blood draw. Snippets of
DNA or RNA detected in the blood could be analyzed for the presence of a
tumor; whether it has metastasized and whether it carries mutations for
resistance to specific drugs. Such “liquid biopsies” may now be within
reach. Kathy Collins, professor of biophysics, biochemistry,
and structural biology is launching a startup called KarnaTeq to develop
and market a technology to increase the diagnostic power of this new
Cancer cells commonly shed bits of DNA into the blood.
In several recent cancer clinical trials, researchers isolated DNA from
patients’ blood and amplified it for analysis. In a DNA study from one
specialized type of treatment, they were able to identify most of the
treatment-resistant mutations that had been detected through
conventional, invasive biopsies. In fact, DNA sequencing revealed some
mutations that the original biopsies had missed, the scientists
But even a diagnostic tool as promising as this should
be more sensitive and informative in order to fulfill the goal of
personalized medicine, says Collins. With support from the Bakar Fellows
Program, she is developing new techniques to scrutinize the total
content of RNA in blood — a strategy that she thinks may add vital clues
missed by DNA analysis.
“RNA is DNA in action,” Collins says.
While DNA holds the blueprint for making all the proteins in the body,
it hands off to RNA only the instructions that the cell needs. As a
result, this “messenger RNA” carries the up-to-date information on
cells’ conditions and needs.
“Sequencing RNA from liquid
biopsies will allow us to see not only the state of a cancer but also
the molecular signatures of any normal tissue that is in trauma from a
treatment,” she says. “Tissue stress is critical to tuning therapy. DNA
alone won’t yield this information.”
In other words, DNA
sequences may be easier to find, she says, but they don’t hold all the
clues. “We don’t want to bias our understanding by getting only a
To analyze gene sequences retrieved from blood,
researchers use a relatively large blood draw. They isolate and amplify
the genetic material that has made its way into the blood. With current
technology, they can generate millions of individual DNA molecules for
analysis, but not all of the RNA.
So far, Collins says, only
messenger RNA from intact cells can be analyzed comprehensively. “A
profile of other types of RNA such as non-coding RNA and RNA from
pathogens would give an unbiased, ‘wide-field’ snapshot of current
has developed a new technology that employs a type of enzyme that she
has studied for more than 20 years. It is called a reverse transcriptase
because it can translate, or transcribe, RNA into DNA — the reverse of
the classic “Watson and Crick” DNA to RNA process.
HIV and other
retroviruses use their own reverse transcriptase to transcribe their RNA
into DNA and then integrate it into a host’s DNA strands. The invaded
cell then becomes an agent of its own destruction, blindly replicating
the virus’s genetic instructions along with its own, enabling the virus
to multiply and spread.
Through modifications of an ancient
reverse transcriptase, Collins can retrieve a comprehensive inventory of
RNA. Because of the unique way the enzyme engages RNA molecules, it can
access folded strands generally invisible to other techniques. The
transcribing process captures more of the RNA than other methods and is
She is particularly interested in applying the
new strategy to study RNA held in bubble-like vesicles, called
exosomes, secreted by cancer cells into the blood. Very little is known
about them, but many scientists suspect that DNA, RNA and other
molecules packed inside the vesicles can provide unique insights into
cancer’s progress in a patient.
With guidance from Bakar Fellows
mentors, Collins aims to advance research on exosomes and other
potential troves of genetic information, and expects her new RNA
analysis technology will be useful in a range of basic research and