From UCSF, New Sequencer Reveals Cancer Blueprints, Cell By Cell

Xconomy San Francisco — 

Cells within a single tumor can have a variety of genetic fingerprints. Understanding that variety is likely a key to fighting cancer in the near future.

A new biotech firm has developed a device that analyzes tumors cell by cell. Single-cell analysis is nothing new. But Mission Bio, of South San Francisco, says it taken the technology a step forward. Instead of reading the code, or RNA, that comes from the switched-on genes inside each cell, Mission Bio’s machine reads each cell’s DNA—the full blueprint. Others including industry leader Fluidigm (NASDAQ: FLDM) are racing to produce DNA readouts from single cells, as well, but Mission Bio says it has produced a cheaper, faster machine that can analyze up to 10,000 cells in a single run.

The firm, spun out of the University of California, San Francisco laboratory of Adam Abate, said today it has raised a Series A fund of $10 million led by the Mayfield Fund.

There are at least two big reasons to move from single-cell analysis of RNA, which gives a snapshot of the proteins a cell might be producing, to DNA. Cancer is driven by changes in DNA, and a growing number of drugs are aimed at those mutations to kill the cancer cells, while leaving normal cells alone. What’s more, DNA is one of nature’s most resilient materials, much better suited than RNA to the clinical work of obtaining patient samples, storing them outside the body, and potentially shipping them around.

For cancer, the FDA this year approved the first-ever drug to treat disease based upon its underlying genetic signature, but more could be on the way. Even when targeted treatments work, however, the tumor often has ways to rebound, and expensive treatments can end up bringing relatively short relief.

“Our early users are in translational medicine at cancer centers,” says Mission Bio CEO Charlie Silver. “They want to know with better precision what’s in the tumor, then figure out which drugs to treat the patient.”

Mission Bio’s system, called Tapestri, can analyze several thousand cells in one go by channeling the cells in a microscopic conga line through a groove on a microchip. Each cell, tagged with a unique barcode, travels in its own droplet of water that acts as a tiny test tube. Sending 10,000 cells through the microchip—a single run—takes about four hours, says Silver.

Mission Bio says its machine will help researchers investigate different types of cancer and potentially develop drugs that attack tumors more precisely. To save time and keep costs relatively low—$795 a run—it does not sequence the entire DNA of a cell. (The Tapestri machine costs $79,500.) Due this December, its first product will look for 19 genes associated with acute myeloid leukemia. After that, Silver says, Mission Bio will create further tests customized for other cancer types.

Silver also envisions gene editing researchers using the analyzer to detect whether their DNA edits have gone awry.

One beta tester, Koichi Takahashi, a leukemia specialist at MD Anderson Cancer Center in Houston, says he sent bone marrow samples from three patients to Mission Bio. The three samples each were taken at three different times: when the patient was diagnosed, when the cancer went into remission, and when it recurred.

For one patient, the analysis showed three different key mutations. At times each mutation was present on its own in some cells. In other cells, the mutations appeared in combination. Some cells had homozygous mutations, that is, in both copies of their DNA—human cells have two copies—while other cells just had single-copy, or heterozygous, mutations.

“This opens up a new question,” Takahashi says. “Are these homozygous cells more resistant to chemotherapy? Or are they more sensitive to chemotherapy? No one really knows. We never had a chance to visualize the mutation composition at this level of single cell resolution.” (Takahashi says he plans to buy Tapestri for his lab. He does not have financial ties in the company.)

There’s a fine line for the Tapestri system’ use: It is not yet approved to guide doctors toward the best drugs to treat individual patients; those kinds of cancer tests, which sequence tumor samples but not on a cell-by-cell basis, have been on the market for years.

But Takahashi says that he would like to use Tapestri to detect lingering cancer in people who otherwise seem to be in remission. These stubborn holdout cells are called minimum residual disease, and they are suspected to be the reason why patients relapse. Finding them and decoding their DNA could help doctors make treatment decisions. Silver says this use, if taken as one of several data points that steer a patient toward, say, a bone marrow transplant, would be within regulatory bounds.

That said, Takahashi is not sure the current firepower of the system is adequate for confident identification of minimum residual disease. (Silver begs to differ.) But Takahashi doesn’t think it’s too far off: “If a single cell platform can analyze a much larger number of cells and detect one abnormal cell, it would have a unique position.”

Image of melanoma cells by the National Cancer Institute.