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Proteintech Genomics Targets Intracellular Proteins in Single-Cell, Multiomic Assays

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NEW YORK – Proteintech Genomics, a subsidiary of Chicago-based antibody manufacturer ProteinTech, has arrived on the market with its first product, which enables the simultaneous detection of intracellular proteins and whole transcriptome gene expression in single-cells.

Launched last month, the MultiPro Immune Profiling Antibody Cocktail is designed to work with 10x Genomics' Gene Expression Flex assay, leveraging that company's ability to detect cell-surface markers to drill down further into the cell to find targets.

Targeting 53 proteins found at multiple levels within a cell, the assay is validated to work in fixed samples off peripheral blood mononuclear cells. Targets include nuclear, cytosolic, secreted proteins such as interleukins, and cell-surface markers. The assay has also been developed with the blessing of 10x under a compatible product partnership, and the firms have a comarketing agreement.

"Our first product is really exciting," said Proteintech Genomics CEO Kit Nazor. "But it's also only our first product. We want to increase [the number of targets] by tenfold." The firm is also working with 10x on developing antibodies for use in spatial assays on the Xenium platform.

With access to antibodies validated for thousands of human proteins, Proteintech Genomics may be situated to pull that off. Already, it has a library of approximately 50 additional antibodies that can target proteins in live cells. "There's really no imposed upper limit," Nazor said. "It's just about identifying antibodies that work in those assays."

Based in San Diego, Proteintech Genomics was established in April last year as an offshoot of Proteintech. The parent company has been making antibodies since 2001 with the goal of creating antibodies for every protein in the human genome. To date, its catalog covers approximately 13,000 proteins, Nazor said. Currently, the Human Proteome Project predicts that there are 19,778 proteins encoded by the human genome, more than 18,000 of which have been found.

Nazor's outfit has 10 employees and is hiring for several positions with the expectation to double by the end of 2024. He noted that Proteintech Genomics has enough cash to last about four years.

The MultiPro reagents are enabled by the promotion of the Flex as 10x's assay of choice for the Chromium, single-cell sequencing platform. The new assay was designed for use with fixed and permeabilized samples, meaning oligo-barcoded antibodies can now reach proteins below the surface of cells that will later be isolated for gene expression profiling. Previously, 10x's single-cell gene expression assays could only detect surface proteins with such barcodes.

"There have been previous academic publications that demonstrate the ability to do intracellular protein detection and gene expression, but the scalability and data quality of those has been challenging to roll out to the larger community," said Peter Skene, a researcher at the Allen Institute for Immunology, who said he is in the market for ways to get protein and RNA data to get a better picture of cell types and their functional states.

"The work from companies such as Proteintech Genomics putting it into production scale and doing validation will really make this technology and the ability to make these measurements available to the broader research community," he said.

Flow cytometry can pick out cells based on protein markers but is lower throughput. Nazor recalled being a grad student and picking cells one by one, putting them into wells, and doing single-cell sequencing that way. Mass Cytometry, especially from Standard Biotools (formerly known as Fluidigm) could select cells based on a comparable number of protein markers, however, those cells are not then available for transcriptomics.

Newer methods, such as NanoString's GeoMx Digital Spatial Profiler, can provide data on the whole transcriptome as well as approximately 570 proteins, but it does not offer true single-cell resolution.

The combo of Proteintech antibodies and 10x's Flex assay "is a game changer," Peter Smibert, VP of biology at 10x Genomics, said in a statement. He is also the inventor of CITE-seq, which underpins the technology that allows barcoded antibodies to be analyzed as part of single-cell sequencing.

The MultiPro cocktail comes in packs of four reactions with a list price of $2,800, or $700 per reaction. This is done to match the 10x Flex assay, which also comes in four- or 16-sample configurations.

Nazor said the cocktail is developed and optimized for peripheral blood mononuclear cells "but can be used for studying immune cells in any context."

"We also have the capacity to build on that and manufacture custom panels," he said. This can only be done at a certain scale, but with the right volume commitment, additional antibody content that is developed by Proteintech or even provided by the customer could be included.