Glyphic Biotechnologies
| Glyphic Biotechnologies | |
|---|---|
| Industry | Proteomics, protein sequencing |
| Founded | 2021 |
| Founders | Joshua Yang, Daniel Estandian (with Edward Boyden as scientific founder) |
| Headquarters | Berkeley, California |
| Products | Protein Sequencing by Expansion (ProSE) |
| Website | glyphic.bio |
Glyphic Biotechnologies is a company in Berkeley, California, that is developing a way to read the amino acid sequence of a protein one molecule at a time. It was founded in 2021 as a spinout from the laboratory of Edward Boyden at MIT.[1][2] Its method, called Protein Sequencing by Expansion (ProSE), turns a protein into a molecule in which the amino acids are spaced out along a linker, then reads that molecule by passing it through a nanopore.[2] Public documents from its first five years describe at least three different ways of getting from a protein to a readout.
Origins
TechCrunch reported on July 26, 2021 that Glyphic had raised a seed round of $6 million and was starting in Berkeley. The founders were Joshua Yang, chief executive, and Daniel Estandian, chief technology officer, both from Boyden's laboratory, with Boyden as scientific founder.[1]
Method over time
The 2021 account was optical. Standard protein sequencing, TechCrunch explained, identifies the amino acid at the end of a chain, removes it and repeats, but the neighboring residue interferes with the identification. Glyphic's version detached the end amino acid first and then tethered it to a known molecule, ClickP, developed by Estandian, so that a single stationary amino acid could be recognized with single-molecule microscopy. Binders specific to each amino acid were still being engineered. The company's target was "millions to tens of millions" of proteins a week, compared with "tens of thousands" for existing machines.[1]
Federal grant records show the plan changing. Glyphic's Small Business Innovation Research awards from the National Institutes of Health include one of 2022 for "iterative isolation and identification of N-terminal amino acids" and one of 2023 for sequencing by "barcoding of N-terminal amino acids". The second describes a "Next-Generation" strategy in which each of the 20 amino acids is cleaved off, captured by a specific antibody and tagged with two DNA barcodes, one naming the source protein and one the position, so that ordinary DNA sequencers can read the result.[3][4]
The award of 2026 is for "resolving individual amino acids via commercially accessible nanopores". Its summary gives the reason for the change: native proteins do not travel easily through commercial nanopores, and a nanopore cannot tell amino acids apart while they sit inside a protein. Glyphic's answer is to separate the amino acids in space, which removes the interactions between neighbors that blur the signal, and to read the resulting "biopolymer" through existing nanopores while a second read of its backbone checks quality. The summary names a first commercial unit for peptides of about 10 amino acids, aimed at immunopeptidomics, the study of the peptides that cells present to the immune system.[5]
ProSE
The company's site describes three steps. Proteins and peptides receive an initiating linker at one end. Amino acids are added to the linker one at a time and spaced evenly in their original order, which builds the "ProSE Molecule". The molecule then passes through a nanopore, "where distinct electrical signatures from each amino acid reveal the protein's sequence."[2] It calls the result "the first truly de novo high-throughput proteome sequencing technology" able to discriminate all 20 amino acids and post-translational modifications.[2]
A patent assigned to the company, US 12,259,393, "Protein sequencing via coupling of polymerizable molecules", was filed on April 4, 2024 and granted on March 25, 2025. It describes attaching polymerizable molecules to the amino acids of a peptide in an intramolecular expansion process and says that analysis may proceed by "sequencing via a nanopore or nanogap".[6] An earlier MIT patent on single-molecule protein and peptide sequencing, naming Boyden and Estandian among its inventors, was filed in January 2020 and granted on November 15, 2022.[7]
The name has an unrelated cousin. Roche's sequencing by expansion converts a DNA strand into a surrogate molecule 10 to 100 times longer before reading it through a pore, and it works on DNA.[8]
See also
References
- ^ a b c Devin Coldewey (July 26, 2021). "Glyphic Biotechnologies raises $6M to accelerate protein sequencing by orders of magnitude". TechCrunch.
- ^ a b c d "Glyphic Biotechnologies". Glyphic Biotechnologies. Retrieved October 25, 2026.
- ^ "Single-molecule protein sequencing by iterative isolation and identification of N-terminal amino acids". NIH RePORTER. National Institutes of Health. 2022.
- ^ "Single-molecule protein sequencing by barcoding of N-terminal amino acids". NIH RePORTER. National Institutes of Health. 2023.
- ^ "Single-molecule protein sequencing: resolving individual amino acids via commercially accessible nanopores". NIH RePORTER. National Institutes of Health. 2026.
- ^ "US12259393B2: Protein sequencing via coupling of polymerizable molecules". Google Patents. March 25, 2025.
- ^ "US11499979B2: Single-molecule protein and peptide sequencing". Google Patents. November 15, 2022.
- ^ "Roche invests in Stratos Genomics for further development of the Sequencing by Expansion (SBX) method applied to single molecule nanopore sequencing". BioSpace. June 26, 2014.