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Boston Area Startup to Develop and Market MIT Scientist s Cell-based cDNA Microarrays

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Sharing a first name and a vision, Whitehead Fellow David Sabatini and former McKinsey & Company consultant David Chao are starting an as-yet unnamed company to commercialize cell-based gene expression microarrays.

The startup, which is likely to be based in the Boston area, plans to commercially develop and market the cell-based microarrays that Sabatini invented in his lab at the Whitehead institute.

The arrays, which Sabatini and a colleague, Junaid Ziauddin, described in a May 3 Nature article, consist of mammalian cells on a glass slide that take up and express particular cDNA strands. The researchers made them by first spotting the array with 192 different cDNAs mixed with an aqueous gelatin, then after drying, exposing the DNA spots to a lipid transfection reagent, and placing the slide in a culture dish of mammalian cells in a medium.

This process would cause a “lawn” of mammalian cells to grow up on the array, with the cells over the cDNA spots taking up the cDNA and becoming expression vectors for it. Since the cDNA was tagged with a green fluorescent protein, the resulting array would consist of green fluorescent clusters.

Users of this array can observe the changes in cell phenotype that result from the expression of a particular cDNA. In the Nature article,Sabatini and Ziauddin screened an array for cDNAs that induced apoptosis by looking for cells on the array that showed abnormal morphological patterns. The researchers tested these fragmented and unusual cells for different proteins, and found one that expressed CD36, a cell-surface protein with cell recognition and adhesion properties.

Sabatini and Ziauddin have also demonstrated that these arrays can be used to identify receptors for a compound. Sabatini and Ziauddin tested the microarrays to see if they could identify receptors for the immunosuppressant FK506 in the cells. They spotted expression vectors for FKBP12, a protein that interacts with FK506, onto the array. Then after growing the cells, they added radio-labelled FK506 to the array. The cells with FKBP12 expression all showed FK506 binding when the researchers used autoradiographical emulsion to detect it.

These arrays offer advantages over non-cell arrays in that they can be used to study protein expression without having to go through the protein separation step, Sabatini said. They can also be used to detect membrane proteins and their relationship to gene expression, since the cells on the arrays are live.

“It’s a convenient way of making a protein microarray,” said Sabatini.

Since publishing the research, Sabatini has been working in his lab to make arrays that have the whole genome on three chips, or ten thousand cell-clusters per array. He is also trying to get the arrays to express phenotypic changes that result from loss of function, not just gain of function.

Sabatini also said academics have been contacting him regarding collaborations to use the cell arrays for particular projects, and companies have shown interest in using the arrays for the drug discovery process.

“There’s been a lot of commercial interest in us,” said Sabatini.

Chao, who has a PhD in Biology from MIT, is currently raising initial seed funding for the company.

— MMJ

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