After a year devoted to incubating their “living” microarrays business, Whitehead fellow David Sabatini and his business partner David Chao are now ready to talk. Their fledgling venture, named Akceli, is focused on commercializing the arrays that Sabatini described in a Nature paper last spring — biochips spotted with clusters of cells, each expressing a different cDNA.
The two Davids have raised $6.5 million in a series A round, with investor Atlas Venture and a significant investment from Apple Tree Partners. In October the company moved into 8,000 square feet of lab space in Cambridge and started to work — so far with 13 employees, but “we are growing quickly,” said Chao, who is Akceli’s president.
These living arrays sprang out of Sabatini’s academic research, in which he was trying to improve expression cloning techniques. Instead of adding cDNA to cells in a dish, he spotted cDNAs onto a glass slide — so they could be identified by their position — and then added the cells, a process he called “reverse transfection.” After taking up the DNA, the cells start making the encoded protein. A compound can then be added and its effect on the cells or its binding to the protein inside be tested. Detection often requires as little as a microscope or a scanner, and Chao believes that almost any of the standard cell-based readouts are possible. “It’s a very inexpensive and very scalable technique,” he said.
The commercial applications in drug discovery are also evident, according to Chao. The biochips could be used to identify, for example, unknown targets for specific drugs or compounds. Since the Nature publication, which used up to 192 different cDNAs, the company has ramped up the number of spots per slide to 6,000 and says 10,000 are possible. Besides scaling them up, it has also made the arrays more robust and consistent, Chao said.
Apart from improving the published slide-based array type, Akceli has since also developed another, plate-based format, which allows it to screen many compounds at once. It can print up to 49 different cDNAs in a single well of a 96-well plate or several hundred in the well of a 24-well plate. These “arrays of arrays” would be suitable to screen compounds against entire classes of proteins to determine their selectivity. “It’s compatible with all of the liquid handling robotics and automation that you would like to be able to use with any high-throughput technology,” said Chao.
In the coming months, the company wants to continue to develop the technology but also start to exploit it — both in-house and through partnerships. One goal is to develop knock-down arrays, where each cell cluster is deficient in one gene instead of expressing an additional one, and to develop methods that make the arrays suitable for many different cell types — so far Akceli has successfully used only five — including primary cell lines, which are difficult to transfect.
On the in-house discovery front, Akceli is now concentrating on a number of target classes, testing the selectivity of compounds, finding ligands for receptors, “as well as doing other types of screens for genes that cause particular phenotypes of interest,” Chao said.
The company is also looking for partners — different ones for different purposes. “We are in discussion with several firms to help commercialize the technology,” said Chao — one that would manufacture, market and distribute the arrays for them.
But Akceli would also like to marry its technology to other systems, he said. “The idea is to couple our format with complementary technologies so that together with our partner we can create a platform that’s much more powerful than either one alone.” These could be detection instrumentation or readout systems companies.
Pharmaceutical companies are the third suitable partner, but this is further down the road. “We would like to work internally to really expand the technology and increase its power before we go out to these pharmaceutical and biotech partners,” said Chao.