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Harvard Spinout 1CellBio Seeks Ideas for Applications of Targeted Single-Cell Tech

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NEW YORK – Single-cell library prep firm 1CellBio has launched an early-access program in a bid to develop applications based on new targeted cell selection and sequencing capabilities that could expand sales of its droplet-based platform.

The Boston-area firm has begun talks with about a half-dozen potential partners, CEO Colin Brenan said. The program comes as the firm is looking to strike out on its own and find collaborators other than HiFiBio, a drug development company also founded by Brenan and the Harvard University researchers who initially developed the inDrop single-cell technology.

The two firms recently collaborated with researchers from the Pasteur Institute and ESPCI Paris on a paper published March 30 in Nature Biotechnology, showcasing the ability to sort cells with assayable characteristics prior to sequencing — specifically paired antibody V genes in B cells from immune repertoires. 

"We want to see what the community response is to [the platform]," Brenan said, "and what the applications could be outside of antibody discovery."

"Their priority is how they can differentiate themselves from [companies like] 10x Genomics and Bio-Rad," said Ken Lau, a researcher at Vanderbilt University who has collaborated with 1CellBio on product development. "They're trying to generate new ideas, new assays, new applications." The platform is "definitely more open than 10x, which is a box where you put in a kit," he said. "You clan play around a lot."

"It's a semi-custom business right now, but there's intent to establish a standard product," Brenan said. "We could be selling bioassay kits and the backend sorting is all standardized. I don't know yet which way we're going to go. But certainly those options are on the table."

Launched to commercialize inDrop single-cell sequencing library preparation technology developed by Harvard's Allon Klein and David Weitz, 1CellBio has always offered an open, customizable platform. The new cell targeting technology is one example of how the company is able to improvise to meet particular research needs. HiFiBio has been using a version of 1CellBio's platform, dubbed CelliGo, as part of its antibody therapeutics discovery program. 

For the Nature Biotechnology study, the firms collaborated on developing two ways to select IgG antibody repertoires from B cells using microfluidics, which were later sequenced. They found ways to sort droplets containing antibodies bound to soluble antigens as well as droplets with antibodies bound to reporter cells expressing antigen.

The method enabled screening based on functional properties of the cell, which in theory could be determined by different assays. "This is different from conventional approaches where a cell subpopulation is first sorted based on a fluorescent label that identifies the cell type and then assayed," Brenan said. "Our approach efficiently and directly identifies the small subpopulation of cells with the functional properties of interest in a population of millions of cells. 

Antibody-secreting cells could also be targeted with assays such as "binding to soluble antigens, cross-reactivity or specific binding (using multiple soluble antigens), binding to cell-surface targets (on both bacterial and eukaryotic cells), inhibition of target activity, cellular internalization, opsonization, and functional modulation of cellular signaling pathways," the authors wrote.

But Brenan envisions even broader applicability, hence the early-access program. "If HiFiBio can do it, I can offer it to others in a similar format," he said.

He declined to disclose who the firm is in talks with, but said additional applications could include tumor profiling, T cell receptor profiling, rare cell sequencing, cytotoxic assays, novel materials discovery, and single-cell screening and sequencing of complex libraries. Marine and environmental biology were two more directions he was hoping the technology could expand into.

For interested parties, 1CellBio offers lots of informational support, despite having limited resources as a smaller company, and is open to new ideas, Lau said. His lab completed a collaboration with 1CellBio on an indexing scheme to improve data quality when using the technology with the Illumina NovaSeq platform. "They provided us with what they worked on in terms of conceptualization of the standard primer scheme. We did all the experiments, all the tests, all the redesign." Lau said the company did not provide financial or material support. "The reagents we use are all sourced from other places," he said, adding that 1CellBio doesn't offer reagent kits.

Technically, researchers could even use a library prep platform other than inDrop after using 1CellBio's sorting microfluidics. However, Brenan noted they would have to develop and validate the protocols on their own and the firm would not be able to support a different downstream library preparation.

Lau said he has a good working relationship with 1CellBio. Separately, he noted that it felt like his academic lab was performing R&D for the firm, rather than having that take place internally at the company. He suggested that the technology development was based on mutual interests of the company and customers.

"We have both internal and external R&D programs whereby the internal projects are mostly focused on improving our manufacturing processes and the external projects are grounded in new product ideas that have come from interactions with our customer base," Brenan said. "It is a path we decided to follow early on in the company's history because we have learned from past commercial experience of the value of being close to and learning from our customers."

Brenan added he was satisfied with the number of discussions with potential partners, especially given the COVID-19-induced slowdown of research not related to the pandemic. He even suggested that 1CellBio's tech could be instrumental in learning more about COVID-19 and the human immune system response. In addition to finding antibodies, the firm's technology "could look for virus-cell interactions on a single-cell basis," he said. "Or we could help explore potential drug targets to block or neutralize the virus. With conventional methods, it's really hard to do that."

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